# ent

id: cord-021552-6jbm869r
type: DNA
entity:
  human caliciviruses family Caliciviridae human influenza viruses family Orthomyxoviridae human polioviruses and human rhinoviruses family Picornaviridae


id: cord-021552-6jbm869r
type: DNA
entity:
  human rotaviruses family Reoviridae b Recurrent Viral production often very pronounced initially is recurrent when the virus persists


id: cord-021552-6jbm869r
type: DISEASE
entity:
  Arthralgia encephalitis hematemesis hematuria hemolytic uremia hemorrhagic fever hemorrhagic pneumonia hemorrhagic


id: cord-021552-6jbm869r
type: DISEASE
entity:
  gastrointestinal infection encephalitis hepatomegaly keratoconjunctivitis lymphoma myelitis neuralgia


id: cord-007735-ejvv2lxv
type: PROTEIN
entity:
  Tumour necrosis factor alpha MHC1 Major histocompatibility complex class 1 BAL Bronchoalveolar lavage 1


id: cord-263312-x7f0hn7f
type: PROTEIN
entity:
  Gram negative bacteria Vibrio cholerae Serratia marcescens Pseudomonas aeruginosa Salmonella typhimurium Chlamydia spp Burkholderia cepacia Yersinia pseudotuberculosis Francisella


id: cord-263312-x7f0hn7f
type: TAXON
entity:
  flies Candida albicans Aspergillus fumigatus Aspergillus hyphae Cryptococcus neoformans Cunninghamella


id: cord-262585-5vjqrnwh
type: DISEASE
entity:
  herpes simplex virus 2 Herpes simplex virus 2 ICP34 5 confers neurovirulence by regulating the type I interferon response An N terminal arginine


id: cord-262434-q4tk96tq
type: CL
entity:
  red squirrels Sciurus vulgaris Temporal and serological findings An increasing danger of zoonotic orthopoxvirus


id: cord-269505-7g8lio9l
type: ORG
entity:
  Ecosystem Functioning and Human Wellbeing an Ecological and Economic Perspective Ecosystems and Human Well Being Current State


id: cord-289443-46w52de3
type: PROTEIN
entity:
  ankyrin repeat domain 30A ANKRD30A CD4 microtubule associated protein 4 MAP4 nucleoporin 153 kDa NUP153


id: cord-289443-46w52de3
type: PROTEIN
entity:
  proteolytic fragments B2M β2 microglobulin BLMH bleomycin hydrolase CALR calreticulin CD40LG CD40 ligand


id: cord-289443-46w52de3
type: PROTEIN
entity:
  cellular proteases ACE2 angiotensin converting enzyme 2 DARC Duffy blood group atypical chemokine receptor MX1 myxovirus resistance 1 SSD sterol sensing domain TFRC transferrin receptor TLR4 Toll


id: cord-289443-46w52de3
type: CL
entity:
  natural killer T iTCR invariant TCR LGMN legumain LNPEP leucyl cystinyl aminopeptidase NCF neutrophil cytosol


id: cord-289443-46w52de3
type: DISEASE
entity:
  HIV 1 replication HIV 1 capsid cyclophilin interactions determine nuclear import pathway integration targeting and replication efficiency This


id: cord-299828-fb84rtmx
type: ORG
entity:
  National Wildlife Health Center Wildpro National Biological Information Infrastructure Wildlife Disease Information


id: cord-002423-1u44tdrj
type: TAXON
entity:
  Flaviviridae Hepadnaviridae Herpesviridae Orthomyxoviridae Papillomaviridae Paramyxoviridae Parvoviridae


id: cord-104317-t30dg6oj
type: WORK_OF_ART
entity:
  An Ecological Framework of the Human Virome Provides Classification of Current Knowledge and Identifies Areas of Forthcoming Discovery


id: cord-104317-t30dg6oj
type: ORG
entity:
  an Suppression of Root Nodule Formation by Artificial Expression of the TrEnodDR1 Coat Protein of White


id: cord-104317-t30dg6oj
type: WORK_OF_ART
entity:
  The Natural History of Hepatitis C Virus HCV Infection Screening Blood Public Health and Medical Uncertainty Current


id: cord-104317-t30dg6oj
type: WORK_OF_ART
entity:
  Our Current Understanding of Mutualism Transmission Modes and Evolution of the Parasitism Mutualism Continuuma


id: cord-104317-t30dg6oj
type: WORK_OF_ART
entity:
  Taking it Personally Personalized Utilization of the Human Microbiome in Health and Disease Immunity


id: cord-276637-re9c3e0b
type: GGP
entity:
  seabirds Procellariformes Phaethontiformes Suliformes Charadriiformes Sphenisciformes Pelicaniformes


id: cord-102383-m5ahicqb
type: EVENT
entity:
  Genetic Variability and Evolution of Hepatitis E Virus Genomic Analysis of the Emergence Evolution and Spread of Human Respiratory RNA Viruses Host Factors in Positive Strand RNA Virus Genome Replication


id: cord-330590-nu8ckeud
type: CELL_TYPE
entity:
  mammalian super tree hosts Bininda Emonds et al 2007 with the picante package We include the body mass litter size number of litters per year and trophic guild


id: cord-000546-0hobwqpe
type: GGP
entity:
  adenylate cyclase Leppla 1982 Both LF and EF are essential for the lethal effects of anthrax Pezard et al 1991 which culminates in vascular failure and septic shock like death An important unanswered question is how do LF and EF with such seemingly disparate enzymatic


id: cord-048325-pk7pnmlo
type: ORG
entity:
  the Transmission of Infectious Diseases Transmission and Dynamics of Tuberculosis on Generalized Households Epidemic Diseases and Host


id: cord-048325-pk7pnmlo
type: ORG
entity:
  The Differential Infectivity and Staged Progression Models for the Transmission of HIV Modeling the Spread of Influenza


id: cord-290253-hxxizipk
type: PROTEIN
entity:
  nuclear Adh SOD Amyrel RpL32 A random starting tree was used with a relaxed uncorrelated lognormal molecular clock Each of the partitions used a HKY substitution model


id: cord-335774-15fhg8o9
type: DISEASE
entity:
  infectious to humans but incorrectly dismissed due to a lack of sequencing Conversely additional orthohantaviruses or viral


id: cord-019068-6j42euvc
type: CELL_LINE
entity:
  JT Hoeg M Grygier Y Fujita H Glenner J Olesen 5 8 Ascothoracida Copebarnacles These are uncommon parasites


id: cord-019068-6j42euvc
type: CL
entity:
  algae planktotrophic larvae and metamorphose into myses which look like tiny adults and feed on algae


id: cord-019068-6j42euvc
type: CL
entity:
  pilosus Crustacea Isopoda Gnathiidae from the east coast of South Africa The Salmon Louse Lepeophtheirus salmonis Copepoda Caligidae life cycle has only two chalimus stages The fish parasite Argulus


id: cord-019068-6j42euvc
type: DISEASE
entity:
  embryonic stage Sheina orri Myodocopa Cypridinidae an ostracod parasitic on the gills of the epaulette shark Hemiscyllium ocellatum Elasmobranchii Hemiscyllidae Metazoan parasites


id: cord-348819-gq7lp931
type: DISEASE
entity:
  human immunodeficiency virus 44 and royalsocietypublishing org journal rstb Phil Trans R Soc B 374 20190014


id: cord-255181-du6rqc6i
type: DISEASE
entity:
  influenza 1918 Asian influenza 1957 and Hong Kong influenza 1968 that killed millions of people worldwide Although influenza A viruses


id: cord-270604-u62437dh
type: DNA
entity:
  caliciviruses reptilian crotalus 1 feline calicivirus and San Miguel sea lion virus Smith et al 1998 Etherington et al 2006 the


id: cord-259505-7hiss0j3
type: PROTEIN
entity:
  molecular chaperone 18 macromolcular biosynthesis proteins 17 cytoskeletal proteins 15 signal transport proteins 15 protein degradation 8 chromosome associated proteins 2 ribosomal proteins 2


id: cord-259505-7hiss0j3
type: PROTEIN
entity:
  aldehyde dehydrogenase 9 family member A1 ALDH9A1 glyceraldehyde 3 phosphate dehydrogenase GAPDH alpha enolase


id: cord-259505-7hiss0j3
type: DNA
entity:
  hepatitis B virus posttranscriptional regulatory element Glyceraldehyde 3 phosphate dehydrogenase GAPDH


id: cord-259505-7hiss0j3
type: GGP
entity:
  Kaposi s sarcoma associated herpesvirus KSHV 8 9 Marek s disease virus MDV 10 Epstein Barr virus EBV 11 human


id: cord-320083-0k15w624
type: ORG
entity:
  Cause Actin Cytoskeletal Disruption Antibiotic Resistance Virulence Factors Phenotyping and Genotyping of Non


id: cord-320083-0k15w624
type: WORK_OF_ART
entity:
  Complex Catching a SPY Using the SpyCatcher SpyTag and Related Systems for Labeling and Localizing Bacterial Proteins Acknowledgments IBB Institute for Bioengineering and Biosciences


id: cord-021465-2pj26fmv
type: CL
entity:
  natural outbreaks Eleazer and Hill 1994 Economically significant outbreaks of disease due to EEE virus


id: cord-021465-2pj26fmv
type: DISEASE
entity:
  influenza hemagglutinin Type A influenza viruses in the feces of migratory waterfowl Detection of avian leukosis virus subgroup J using the polymerase chain reaction Multiple alignment


id: cord-018555-3lta1tbp
type: DISEASE
entity:
  zoonotic e g HIV 1 and HIV 2 influenza virus Ebola virus hantaviruses Nipah virus Zika virus and the SARS coronavirus


id: cord-314325-nquov2i0
type: ORG
entity:
  Virus Dynamics Mathematical Principles of Immunology and Virology Emerging Microbial Threats to Health


id: cord-297960-4x1j0iqg
type: PROTEIN
entity:
  CD44 antigen CD44 Serine arginine repetitive matrix protein 2 SRRM2 Myristoylated alaninerich C kinase substrate MARCKS BAG family molecular chaperone regulator 3 BAG3


id: cord-355024-v5lahyw4
type: WORK_OF_ART
entity:
  Safer Water Better Health Costs Benefits and Sustainability of Interventions to Protect and Promote Health Cofactors


id: cord-355024-v5lahyw4
type: WORK_OF_ART
entity:
  the Global Burden of Disease Study Excreta Disposal for Rural Areas and Small Communities WHO Consolidated Guidelines on the Use of Antiretroviral Drugs for Treating and Preventing HIV Infection Large


id: cord-264884-ydkigome
type: DNA
entity:
  P1 and mouse hepatitis virus MHV persistence exemplars Villarreal 2006 Villarreal 2007 Since viruses are ancient numerically dominant and the most diverse biological entities on Earth


id: cord-355239-fc52dn3v
type: CL
entity:
  trophozoites to host extracellular matrix components A novel multidomain mucin like glycoprotein of Cryptosporidium parvum


id: cord-355239-fc52dn3v
type: GO
entity:
  transmembrane heparan sulfate proteoglycans Integral membrane heparan sulfate proteoglycans Glycolipids


# bib

id: cord-000546-0hobwqpe
title: Deconstructing host-pathogen interactions in Drosophila
author: Bier, Ethan
date: 2011-10-06
txt: ./txt/cord-000546-0hobwqpe.txt
cache: ./cache/cord-000546-0hobwqpe.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3255543/
doi: 10.1242/dmm.000406
summary:
  We then focus on three related topics: (1) genome-wide RNAi screens in Drosophila cell lines infected with pathogens to identify host pathways for defense or that are exploited by pathogens (e.g. bacteria, fungi, viruses); (2) classical genetic and RNAi screens conducted in intact flies to delineate host defense pathways that are active in specific tissues (e.g. the gut) or to identify important virulence factors produced by the pathogen; and (3) analysis of the function of specific pathogen virulence factors in an intact organism. In one screen using adult flies, host defense factors that are required to protect against intestinal infection with the opportunistic broad-host-spectrum pathogen Serratia marcescens were first identified by using a large collection of fly lines in which 13,000 individual RNAi molecules were used to knock down target gene expression throughout the organism (Cronin et al., 2009) .

abstract:
  Many of the cellular mechanisms underlying host responses to pathogens have been well conserved during evolution. As a result, Drosophila can be used to deconstruct many of the key events in host-pathogen interactions by using a wealth of well-developed molecular and genetic tools. In this review, we aim to emphasize the great leverage provided by the suite of genomic and classical genetic approaches available in flies for decoding details of host-pathogen interactions; these findings can then be applied to studies in higher organisms. We first briefly summarize the general strategies by which Drosophila resists and responds to pathogens. We then focus on how recently developed genome-wide RNA interference (RNAi) screens conducted in cells and flies, combined with classical genetic methods, have provided molecular insight into host-pathogen interactions, covering examples of bacteria, fungi and viruses. Finally, we discuss novel strategies for how flies can be used as a tool to examine how specific isolated virulence factors act on an intact host.


id: cord-001714-jfawhnsq
title: Bridge hosts, a missing link for disease ecology in multi-host systems
author: Caron, Alexandre
date: 2015-07-21
txt: ./txt/cord-001714-jfawhnsq.txt
cache: ./cache/cord-001714-jfawhnsq.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4509689/
doi: 10.1186/s13567-015-0217-9
summary:
  We illustrate this framework using the example of the transmission of Avian Influenza Viruses across wild bird/poultry interfaces in Africa and discuss a range of other examples that demonstrate the usefulness of our definition for other multi-host systems. Lastly, we present an operational framework to identify potential bridge host populations, using as a case study the ecology of avian influenza viruses at the wild/domestic bird interface in Africa and also giving other multi-host systems examples. As a consequence, the information available on most wild bird species is scarce and has been obtained mostly from by-catch (i.e. captured non-targeted species) of studies investigating AIV in maintenance waterfowl, resulting in small sample sizes that are inadequate to provide epidemiological understanding of the host roles in AIV ecology in Africa [26] . The range of methods available to characterize host competence for AIV and contact patterns between maintenance, potential bridge and target host populations is drawn from the fields of epidemiology and avian ecology ( Table 2) .

abstract:
  In ecology, the grouping of species into functional groups has played a valuable role in simplifying ecological complexity. In epidemiology, further clarifications of epidemiological functions are needed: while host roles may be defined, they are often used loosely, partly because of a lack of clarity on the relationships between a host’s function and its epidemiological role. Here we focus on the definition of bridge hosts and their epidemiological consequences. Bridge hosts provide a link through which pathogens can be transmitted from maintenance host populations or communities to receptive populations that people want to protect (i.e., target hosts). A bridge host should (1) be competent for the pathogen or able to mechanically transmit it; and (2) come into direct contact or share habitat with both maintenance and target populations. Demonstration of bridging requires an operational framework that integrates ecological and epidemiological approaches. We illustrate this framework using the example of the transmission of Avian Influenza Viruses across wild bird/poultry interfaces in Africa and discuss a range of other examples that demonstrate the usefulness of our definition for other multi-host systems. Bridge hosts can be particularly important for understanding and managing infectious disease dynamics in multi-host systems at wildlife/domestic/human interfaces, including emerging infections. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13567-015-0217-9) contains supplementary material, which is available to authorized users.


id: cord-002423-1u44tdrj
author: Geoghegan, Jemma L.
date: 2017-02-08
txt: ./txt/cord-002423-1u44tdrj.txt
cache: ./cache/cord-002423-1u44tdrj.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5319820/
doi: 10.1371/journal.ppat.1006215
summary:
  While this method does not explicitly model host-switching events, it does provide a simple means to compare multiple topologies of virus-host pairs, and accounts for differences in sample size and the fact that several viruses from a specific family can infect a single host species. Across the data set as a whole we found that all virus families displayed relatively large tree topological distances with nPH85 values of !0.6, suggesting that cross-species transmission is widespread, at least at the family-level (Fig 2; S3 Table) . As with the analysis of topological distances, this revealed that cross-species transmission was the most common evolutionary event in all virus families studied here, with co-divergence consistently less frequent (with the possible exception of the Hepadnaviridae-see below), and lineage duplication and extinction playing a much more minor role. To investigate the comparative prevalence of cross-species transmission among viruses we measured the congruence between virus and host phylogenetic trees using a normalized tree topological distance-based approach (nPH85, [14] ).

title:
  Comparative analysis estimates the relative frequencies of co-divergence and cross-species transmission within viral families

abstract:
  The cross-species transmission of viruses from one host species to another is responsible for the majority of emerging infections. However, it is unclear whether some virus families have a greater propensity to jump host species than others. If related viruses have an evolutionary history of co-divergence with their hosts there should be evidence of topological similarities between the virus and host phylogenetic trees, whereas host jumping generates incongruent tree topologies. By analyzing co-phylogenetic processes in 19 virus families and their eukaryotic hosts we provide a quantitative and comparative estimate of the relative frequency of virus-host co-divergence versus cross-species transmission among virus families. Notably, our analysis reveals that cross-species transmission is a near universal feature of the viruses analyzed here, with virus-host co-divergence occurring less frequently and always on a subset of viruses. Despite the overall high topological incongruence among virus and host phylogenies, the Hepadnaviridae, Polyomaviridae, Poxviridae, Papillomaviridae and Adenoviridae, all of which possess double-stranded DNA genomes, exhibited more frequent co-divergence than the other virus families studied here. At the other extreme, the virus and host trees for all the RNA viruses studied here, particularly the Rhabdoviridae and the Picornaviridae, displayed high levels of topological incongruence, indicative of frequent host switching. Overall, we show that cross-species transmission plays a major role in virus evolution, with all the virus families studied here having the potential to jump host species, and that increased sampling will likely reveal more instances of host jumping.


id: cord-003767-9xbu4hnq
author: Slingenbergh, Jan
date: 2019-05-25
txt: ./txt/cord-003767-9xbu4hnq.txt
cache: ./cache/cord-003767-9xbu4hnq.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6631033/
doi: 10.3390/pathogens8020072
summary:
  The synthesis of the findings reveals a predictive virus evolution framework, based on the outerto inner-body changes in the interplay of host environment-transmission modes-organ system involvement-host cell infection cycle-virus genome. Pieced together on this basis was an outer-to inner-body line-up of viruses by organ system or combination of organ systems, guided by the one-to-four virus infiltration score, the corresponding virus organ system tropism, the matching virus transmission modes, length of the infection and shedding periods, infection severity level, and virus environmental survival rate, see Figure 3 and, also, Figure S1d . Pieced together on this basis was an outer-to inner-body line-up of viruses by organ system or combination of organ systems, guided by the one-to-four virus infiltration score, the corresponding virus organ system tropism, the matching virus transmission modes, length of the infection and shedding periods, infection severity level, and virus environmental survival rate, see Figure 3 and, also, Figure S1d .

title:
  Animal Virus Ecology and Evolution Are Shaped by the Virus Host-Body Infiltration and Colonization Pattern

abstract:
  The current classification of animal viruses is largely based on the virus molecular world. Less attention is given to why and how virus fitness results from the success of virus transmission. Virus transmission reflects the infection-shedding-transmission dynamics, and with it, the organ system involvement and other, macroscopic dimensions of the host environment. This study describes the transmission ecology of the world main livestock viruses, 36 in total, a mix of RNA, DNA and retroviruses. Following an iterative process, the viruses are virtually ranked in an outer- to inner-body fashion, by organ system, on ecological grounds. Also portrayed are the shifts in virus host tropism and virus genome. The synthesis of the findings reveals a predictive virus evolution framework, based on the outer- to inner-body changes in the interplay of host environment-transmission modes-organ system involvement-host cell infection cycle-virus genome. Outer-body viruses opportunistically respond to the variation in the external environment. For example, respiratory and enteric viruses tend to be associated with poultry and pig mass rearing. Ruminant and equine viruses tend to be more deep-rooted and host-specific, and also establish themselves in the vital inner-body systems. It is concluded that the framework may assist the study of new emerging viruses and pandemic risks.


id: cord-003806-ctass7hz
title: Recombinant vector vaccine evolution
author: Bull, James J.
date: 2019-07-19
txt: ./txt/cord-003806-ctass7hz.txt
cache: ./cache/cord-003806-ctass7hz.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6668849/
doi: 10.1371/journal.pcbi.1006857
summary:
  These models include evolution arising during the process of manufacture, the dynamics of vaccine and revertant growth, plus innate and adaptive immunity elicited during the course of infection. Here we explore how the combination of evolution during the process of vaccine manufacture and during its within-host dynamics following vaccination could affect the immune responses elicited by a recombinant vector vaccine and reduce its efficacy-the specific interaction between evolution and immunity. Again, the problem is complicated by the limited duration of the infection: reduced antigen production due to vaccine evolution depends not only on interference between the two genomes but also on overall growth and the extent to which it affects the level of immunity to vaccine and vector. The evolutionary consequences should be the same for both types of inferiority, reducing the long term generation of antigen levels within the host, but adaptive immunity would be irrelevant to vaccine evolution during manufacturing and during early growth within the host.

abstract:
  Replicating recombinant vector vaccines consist of a fully competent viral vector backbone engineered to express an antigen from a foreign transgene. From the perspective of viral replication, the transgene is not only dispensable but may even be detrimental. Thus vaccine revertants that delete or inactivate the transgene may evolve to dominate the vaccine virus population both during the process of manufacture of the vaccine as well as during the course of host infection. A particular concern is that this vaccine evolution could reduce its antigenicity—the immunity elicited to the transgene. We use mathematical and computational models to study vaccine evolution and immunity. These models include evolution arising during the process of manufacture, the dynamics of vaccine and revertant growth, plus innate and adaptive immunity elicited during the course of infection. Although the selective basis of vaccine evolution is easy to comprehend, the immunological consequences are not. One complication is that the opportunity for vaccine evolution is limited by the short period of within-host growth before the viral population is cleared. Even less obvious, revertant growth may only weakly interfere with vaccine growth in the host and thus have a limited effect on immunity to vaccine. Overall, we find that within-host vaccine evolution can sometimes compromise vaccine immunity, but only when the extent of evolution during vaccine manufacture is severe, and this evolution can be easily avoided or mitigated.


id: cord-004914-cnz61qjy
title: Cross-Species Pathogen Transmission and Disease Emergence in Primates
author: Pedersen, Amy B.
date: 2010-03-16
txt: ./txt/cord-004914-cnz61qjy.txt
cache: ./cache/cord-004914-cnz61qjy.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7087625/
doi: 10.1007/s10393-010-0284-3
summary:
  This analysis provides the first quantitative attempt to assess the risk of pathogens host-shifting to humans from wildlife populations, a critical step toward predicting disease emergence. Following Davies and Pedersen (2008) , we derived the relationship between evolutionary divergence (representing time to most recent common ancestor from the dated phylogenetic tree of Bininda-Emonds et al., 2007) , and pathogen community similarity (as described above) between each primate pair using generalized linear modeling (GLM) with binomial errors and a logit link function in the statistical package R (R: a programming environment for data analysis and graphics, v. Next, to provide an estimate of the cross-species pathogen transmission risk from wild primates to humans, we constructed a second hotspot map, weighting each primate distribution in proportion to its evolutionary distance from humans, using the nonlinear transformation determined from the GLM model coefficients described above. Population centers in close proximity to regions with high phylogenetic risk of host shifts and human population growth are likely to be foci of disease emergence.

abstract:
  Many of the most virulent emerging infectious diseases in humans, e.g., AIDS and Ebola, are zoonotic, having shifted from wildlife populations. Critical questions for predicting disease emergence are: (1) what determines when and where a disease will first cross from one species to another, and (2) which factors facilitate emergence after a successful host shift. In wild primates, infectious diseases most often are shared between species that are closely related and inhabit the same geographic region. Therefore, humans may be most vulnerable to diseases from the great apes, which include chimpanzees and gorillas, because these species represent our closest relatives. Geographic overlap may provide the opportunity for cross-species transmission, but successful infection and establishment will be determined by the biology of both the host and pathogen. We extrapolate the evolutionary relationship between pathogen sharing and divergence time between primate species to generate “hotspot” maps, highlighting regions where the risk of disease transfer between wild primates and from wild primates to humans is greatest. We find that central Africa and Amazonia are hotspots for cross-species transmission events between wild primates, due to a high diversity of closely related primate species. Hotspots of host shifts to humans will be most likely in the forests of central and west Africa, where humans come into frequent contact with their wild primate relatives. These areas also are likely to sustain a novel epidemic due to their rapidly growing human populations, close proximity to apes, and population centers with high density and contact rates among individuals.


id: cord-005281-wy0zk9p8
title: Viral component of the human genome
author: Blinov, V. M.
date: 2017-05-09
txt: ./txt/cord-005281-wy0zk9p8.txt
cache: ./cache/cord-005281-wy0zk9p8.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7089383/
doi: 10.1134/s0026893317020066
summary:
  In the human genome, this capacity is determined by the portion of chromosomal DNA, which does not contain species-specific protein-encoding sequences and, thus, can basically make a place for novel information that will be modified to reach a new balance. In fact, the scope of the described phenomena is not limited to retroviruses as such, since the ubiquity of retroviral elements in animal genomes, their activity in germline cells [31] , along with the fact that viral replication depends significantly on RNA expression, allow retroviruses to contribute in different ways to the insertion of nonretroviral genes into animal germline cells. Finally, the ability to incorporate parts of the viral genome into the chromosomal DNA of host germline cells can vary strongly among different taxonomic groups of viruses, i.e., orders, families, genera, and even species If insertions of viral sequences remain functionally active in the host cell genome, they can give rise to either proteins that function in a new environment or untranslated RNAs of different sizes.

abstract:
  Relationships between viruses and their human host are traditionally described from the point of view taking into consideration hosts as victims of viral aggression, which results in infectious diseases. However, these relations are in fact two-sided and involve modifications of both the virus and host genomes. Mutations that accumulate in the populations of viruses and hosts may provide them advantages such as the ability to overcome defense barriers of host cells or to create more efficient barriers to deal with the attack of the viral agent. One of the most common ways of reinforcing anti-viral barriers is the horizontal transfer of viral genes into the host genome. Within the host genome, these genes may be modified and extensively expressed to compete with viral copies and inhibit the synthesis of their products or modulate their functions in other ways. This review summarizes the available data on the horizontal gene transfer between viral and human genomes and discusses related problems.


id: cord-007735-ejvv2lxv
title: Immunomodulatory Properties of Defensins and Cathelicidins
author: Bowdish, D. M. E.
date: 2006
txt: ./txt/cord-007735-ejvv2lxv.txt
cache: ./cache/cord-007735-ejvv2lxv.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7121507/
doi: 10.1007/3-540-29916-5_2
summary:
  The expression of certain β-defensins is inducible upon stimulation with bacterial components or pro-inflammatory cytokines and thus these peptides are presumed to be an important component of host defence to infection or inflammation. The difficulties in assessing the role of host defence peptides in vivo are profound, as it is almost impossible to account for synergistic interactions between peptides and other factors, to assess the actual concentrations at the sites of infection and to discriminate the direct antimicrobial activity of peptides from other less direct effects such as enhancement of inflammatory mechanisms (chemotaxis and recruitment of effector cells, enhancement of nonopsonic phagocytosis, etc.). It appears that host defence peptides induce chemotaxis in two ways: first through direct chemotactic activity of PMNs and mononuclear cells mediated through CCR6 and other as yet to be identified receptors and second through inducing chemokine production which would hypothetically increase the numbers of neutrophils and monocytes at sites of infection.

abstract:
  Host defence peptides are a conserved component of the innate immune response in all complex life forms. In humans, the major classes of host defence peptides include the α- and β-defensins and the cathelicidin, hCAP-18/LL-37. These peptides are expressed in the granules of neutrophils and by a wide variety of tissue types. They have many roles in the immune response including both indirect and direct antimicrobial activity, the ability to act as chemokines as well as induce chemokine production leading to recruitment of leukocytes to the site of infection, the promotion of wound healing and an ability to modulate adaptive immunity. It appears that many of these properties are mediated though direct interaction of peptides with the cells of the innate immune response including monocytes, dendritic cells, T cells and epithelial cells. The importance of these peptides in immune responses has been demonstrated since animals defective in the expression of certain host defence peptides showgreater susceptibility to bacterial infections. In the very few instances in which human patients have been demonstrated to have defective host defence peptide expression, these individuals suffer from frequent infections. Although studies of the immunomodulatory properties of these peptides are in their infancy, there is a growing body of evidence suggesting that the immunomodulatory properties of these small, naturally occurring molecules might be harnessed for development as novel therapeutic agents.


id: cord-013837-x95r6bz8
title: New insights into the evasion of host innate immunity by Mycobacterium tuberculosis
author: Chai, Qiyao
date: 2020-07-29
txt: ./txt/cord-013837-x95r6bz8.txt
cache: ./cache/cord-013837-x95r6bz8.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7608469/
doi: 10.1038/s41423-020-0502-z
summary:
  In this review, we describe the emerging role of cytosolic nucleic acid-sensing pathways at the host–Mtb interface and summarize recently revealed mechanisms by which Mtb circumvents host cellular innate immune strategies such as membrane trafficking and integrity, cell death and autophagy. [19] [20] [21] The involvement of the cGAS-mediated DNA-sensing pathway in host anti-Mtb immunity is indicated by the findings that cGAS expression is upregulated and that cGAS is colocalized with mycobacteria in human TB lesions, and its deficiency impairs the induction of type I IFN responses and autophagy in Mtb-infected macrophages. 23 Therefore, specifically targeting mycobacterial ESX-1 products or host regulatory factors might enable the selective regulation of inflammasome and cGAS/STING pathway activation and, hence, contribute to the recovery of the equilibrium between Th1-type cytokine and type I IFN responses in TB patients to improve their anti-Mtb immunity.

abstract:
  Mycobacterium tuberculosis (Mtb) is an extremely successful intracellular pathogen that causes tuberculosis (TB), which remains the leading infectious cause of human death. The early interactions between Mtb and the host innate immune system largely determine the establishment of TB infection and disease development. Upon infection, host cells detect Mtb through a set of innate immune receptors and launch a range of cellular innate immune events. However, these innate defense mechanisms are extensively modulated by Mtb to avoid host immune clearance. In this review, we describe the emerging role of cytosolic nucleic acid-sensing pathways at the host–Mtb interface and summarize recently revealed mechanisms by which Mtb circumvents host cellular innate immune strategies such as membrane trafficking and integrity, cell death and autophagy. In addition, we discuss the newly elucidated strategies by which Mtb manipulates the host molecular regulatory machinery of innate immunity, including the intranuclear regulatory machinery, the ubiquitin system, and cellular intrinsic immune components. A better understanding of innate immune evasion mechanisms adopted by Mtb will provide new insights into TB pathogenesis and contribute to the development of more effective TB vaccines and therapies.


id: cord-014397-7b88ycv8
title: Resistance of livestock to viruses: mechanisms and strategies for genetic engineering
author: Gavora, JS
date: 1996-12-15
txt: ./txt/cord-014397-7b88ycv8.txt
cache: ./cache/cord-014397-7b88ycv8.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2708302/
doi: 10.1186/1297-9686-28-5-385
abstract: nan
summary:
  Thus introduction of new mechanisms of disease resistance in livestock by gene transfer may be viewed as a logical continuation of the creative influence of humans on the evolution of farm animals and birds that could benefit mankind by improvements in food safety and production efficiency. As background for the discussion of the subject, the article deals briefly with coevolution of hosts and parasites and principal elements of virus-host interactions, and reviews past improvement of disease resistance in plants and livestock by conventional breeding and genetic engineering, as well as the potential ''biological cost'' of genetic manipulation. Basic understanding of the parallel evolution of viruses and their hosts provides a useful starting point for the consideration of strategies for genetic engineering of new mechanisms of resistance. Genetic engineering strategies that prevent entry of viruses into host cells would be effective against all three types of viral infection.


id: cord-016717-2twm4hmc
title: How Does Biodiversity Influence the Ecology of Infectious Disease?
author: Vourc’h, Gwenaël
date: 2011-06-28
txt: ./txt/cord-016717-2twm4hmc.txt
cache: ./cache/cord-016717-2twm4hmc.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7121084/
doi: 10.1007/978-94-007-2114-2_13
summary:
  To conclude, we consider that the consequences of the loss of species biodiversity on infectious diseases is still largely unknown, notably due to the lack of knowledge on the dynamics of host-pathogen relationships, especially at the population and at the community level.. To conclude, we consider that the consequences of the loss of species biodiversity on infectious diseases is still largely unknown, notably due to the lack of knowledge on the dynamics of host-pathogen relationships, especially at the population and at the community level.. In this chapter, we investigate how biodiversity influences the ecology of infectious diseases at the intraspecific level (genetic variability of pathogens and hosts) and at the level of communities (species composition). The hypothesis underlying the amplification and dilution effect is that for many diseases, the competence of reservoirs, i.e. the ability to become infected and retransmit the pathogen, varies according to the host species (Haydon et al.

abstract:
  Over the past years, biodiversity has been reduced on an unprecedented scale, while new infectious diseases are emerging at an increasing rate. Greater overall biodiversity could lead to a greater diversity of hosts and thus of pathogens. Yet disease regulation – due to the buffering role of host diversity – is considered to be one of the services provided by biodiversity. In this chapter, we ask how biodiversity is linked to infectious disease. First, we investigate the influence of the biodiversity of pathogens. We highlight that the number of pathogen species is not well known but that new findings are facilitated by the rapid expansion of molecular techniques. We show that, although there is a trend to find higher pathogen richness toward the equator, identifying a global pattern between the richness of all pathogen species and their latitudinal distribution is challenging. We emphasize that pathogen intraspecific diversity is a crucial factor in disease emergence and allows pathogens to adapt to the selective pressures they face. In addition, the selective pressure acting on hosts due to parasite, and reinforced by parasite diversity within hosts seems to be a major evolutionary and ecological force shaping hosts biodiversity. Second, we investigate how the diversity of hosts influences infectious disease ecology. For multi-host diseases, a change in host species richness or abundance can modify the dynamics of local infectious diseases by either reducing (“dilution effect”) or increasing (“amplification effect”) the risk of transmission to the targeted host species. The underlying hypothesis is that, the competence of reservoirs varies according to the host species. The dilution effect has been demonstrated mainly through theoretical work and there have been only few case studies. Regarding the genetic diversity of host, an important issue is: to what extent does a reduction of this diversity impact the ability of the host population to response to infectious diseases? Third, we rapidly examine the role of biodiversity in the treatment of infectious diseases. To conclude, we consider that the consequences of the loss of species biodiversity on infectious diseases is still largely unknown, notably due to the lack of knowledge on the dynamics of host-pathogen relationships, especially at the population and at the community level.. We highlight that work on multi-host/ ulti-pathogen systems should be fostered and that new approaches, such as metagenomic investigations that does not require a priori assumptions, are promising to describe a community of pathogens and their interactions.


id: cord-017008-c7skxte0
title: Emerging Disease and the Evolution of Virulence: The Case of the 1918–1919 Influenza Pandemic
author: Méthot, Pierre-Olivier
date: 2014-08-22
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7121464/
doi: 10.1007/978-94-017-8887-8_5
abstract:
  “Why do parasites harm their host?” is a recurrent question in evolutionary biology and ecology, and has several implications for the biomedical sciences, particularly public health and epidemiology. Contrasting the meaning(s) of the concept of “virulence” in molecular pathology and evolutionary ecology, we review different explanations proposed as to why, and under what conditions, parasites cause harm to their host: whereas the former uses molecular techniques and concepts to explain changes and the nature of virulence seen as a categorical trait, the latter conceptualizes virulence as a phenotypic quantitative trait (usually related to a reduction in the host’s fitness). After describing the biology of emerging influenza viruses we illustrate how the ecological and the molecular approaches provide distinct (but incomplete) explanations of the 1918–19 influenza pandemic. We suggest that an evolutionary approach is necessary to understand the dynamics of disease transmission but that a broader understanding of virulence will ultimately benefit from articulating and integrating the ecological dynamics with cellular mechanisms of virulence. Both ecological and functional perspectives on host-pathogens’ interactions are required to answer the opening question but also to devise appropriate health-care measures in order to prevent (and predict?) future influenza pandemics and other emerging threats. Finally, the difficult co-existence of distinct explanatory frameworks reflects the fact that scientists can work on a same problem using various methodologies but it also highlights the enduring tension between two scientific styles of practice in biomedicine.


id: cord-017819-85x0juiw
title: Biological conservation and parasitism
author: Christe, Philippe
date: 2006
txt: ./txt/cord-017819-85x0juiw.txt
cache: ./cache/cord-017819-85x0juiw.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122491/
doi: 10.1007/978-4-431-36025-4_27
abstract: nan
summary:
  It is, therefore, not surprising that corticosteroid level is measured in many studies in ecology and conservation biology that have evaluated the effect of different environmental and human perturbations on the stress level of wild animals (Creel et al. In contrast, widespread host species that live in high density are exposed to a wide range of parasite species that may affect drastically the population dynamics of these carnivores, suggesting that macroparasites may regulate them at least locally. Interestingly, Allee effects and parasitism have several features in common that are of interest when studying population dynamics in conservation biology (Deredec 2005) . Invasive host species have another advantage if they have invested in strong immune defences in their natural range, which may then subsequently confer a better capacity to control parasites that they may acquire in the introduced habitat.


id: cord-018425-vyiuv5qu
title: Colonization of Parasites and Vectors
author: Bataille, Arnaud
date: 2017-07-28
txt: ./txt/cord-018425-vyiuv5qu.txt
cache: ./cache/cord-018425-vyiuv5qu.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7123297/
doi: 10.1007/978-3-319-65909-1_3
summary:
  In this chapter, we first review some of the major mechanisms by which parasites and vectors could arrive to an oceanic island, both naturally or due to human activities (see Table 3 .1), and the factors that may influence their successful establishment in the insular host community. Probably one of the most famous examples of the impact of introduced parasites on insular wildlife is the decline of the Hawaiian endemic avifauna following the introduction of the avian malaria Plasmodium relictum, avianpox virus, and their mosquito vector Culex quinquefasciatus (Warner 1968; van Riper et al. In order to fully understand the colonization history of hippoboscid fly vectors in Galapagos, large-scale phylogenetic and phylogeographic studies of Haemoproteus parasites, bird hosts, and hippoboscid flies are needed, with an effort to estimate arrival dates where possible.

abstract:
  Colonization comprises the physical arrival of a species in a new area, but also its successful establishment within the local community. Oceanic islands, like the Hawaiian and the Galapagos archipelagos, represent excellent systems to study the mechanisms of colonization because of their historical isolation. In this chapter, we first review some of the major mechanisms by which parasites and vectors could arrive to an oceanic island, both naturally or due to human activities, and the factors that may influence their successful establishment in the insular host community. We then explore examples of natural and anthropogenic colonization of the Galapagos Islands by parasites and vectors, focusing on one or more case studies that best represent the diversity of colonization mechanisms that has shaped parasite distribution in the archipelago. Finally, we discuss future directions for research on parasite and vector colonization in Galapagos Islands.


id: cord-018555-3lta1tbp
title: Host–Symbiont Relationships: Understanding the Change from Guest to Pest
author: Overstreet, Robin M.
date: 2016-01-06
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7123458/
doi: 10.1007/978-3-319-28170-4_2
abstract:
  The several meanings for the term “symbiosis” create confusion, which can be avoided when the author provides details of the interrelationships between the symbiotic organism and the “host” so that a reader can clearly understand what definition is implied in each case. For example, we, as opposed to many other mentioned readers, consider a symbiont as an organism living in an association with another regardless of whether it causes a pathologic response or not, but from our title, the reader may incorrectly infer that we consider a parasite to be different from a symbiont. A symbiont is an organism that uses another organism as a habitat. This chapter discusses the primary associations and associated conflicts involving the terminology. It also provides both differentiation between and conflicting views regarding the interpretation of the terms “infect” and “infest,” “infection” and “disease,” and other terms. Many seemingly harmless symbionts of a wide array of taxonomic groups are triggered to become pathogenic or virulent, and we provide several examples of the provoking (stimulating) triggers, with the understanding that in most cases, the conditions for the triggered activities are much more complex and complicated than presented. Examples of triggers follow: environmental ones like temperature, toxic chemicals (dose), chemotherapeutics, dietary changes, and geographic habits; internal ones like host site, host resistance or susceptibility, and host modifications; and combinations of these and other conditions. We provide examples involving multiple triggers for organisms associated with termites, for an endemic virus being affected by multiple factors and having multiple effects on its commercial penaeid shrimp hosts, and for contrasting variables associated with two exotic viruses in wild and cultured commercial penaeid shrimps with an emphasis on hypothesizing how the pathogenicity developed in these two viruses. The chapter ends by trying to answer the question of why would a symbiont become pathogenic in some hosts and not in others from an evolutionary perspective. It uses two hypotheses to explain the increased virulence.


id: cord-018821-e9oxvgar
title: Sociality, Parasites, and Pathogens in Bats
author: Webber, Quinn M. R.
date: 2016-04-27
txt: ./txt/cord-018821-e9oxvgar.txt
cache: ./cache/cord-018821-e9oxvgar.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7123799/
doi: 10.1007/978-3-319-38953-0_5
summary:
  We identified social network analysis, epidemiological modeling, and interspecific comparative analyses as the most commonly used methods to quantify relationships between social behavior and parasite-risk in bats while WNS, Hendra virus, and arthropod ectoparasites were the most commonly studied host-parasite systems. Although the mechanism inducing increased energy expenditure and arousals by infected bats is still not fully understood (for review see Willis 2015) , variation in social behavior could mediate fungal transmission and growth, especially since affected species tend to hibernate in large colonies or aggregations in caves or mines. We suggest studies employing social network analysis of wild bats, combined with estimates of micro-and macroparasite prevalence, and intensity to disentangle relationships between host social behavior, including fission-fusion dynamics, and the ecology of parasite transmission (for review see Godfrey 2013). Ectoparasite studies have identified links between parasite risk, colony size, and fission-fusion dynamics which have broad implications for understanding how sociality affects host-parasite interactions in bats.

abstract:
  Little is known about the ecology of many of the parasites and pathogens affecting bats, but host social behavior almost certainly plays an important role in bat-parasite dynamics. Understanding parasite dynamics for bats is important from a human public health perspective because of their role as natural reservoirs for recent high-profile emerging zoonotic pathogens (e.g. Ebola, Hendra) and from a bat conservation perspective because of the recent emergence of white-nose syndrome (WNS) in North America highlighting the potential population impacts of parasites and pathogens. Although some bat species are among the most gregarious of mammals, species vary widely in terms of their social behavior and this variation could influence pathogen transmission and impacts. Here, we review the literature on links between bat social behavior and parasite dynamics. Using standardized search terms in Web of Science, we identified articles that explicitly tested or discussed links between some aspect of bat sociality and parasite transmission or host population impacts. We identified social network analysis, epidemiological modeling, and interspecific comparative analyses as the most commonly used methods to quantify relationships between social behavior and parasite-risk in bats while WNS, Hendra virus, and arthropod ectoparasites were the most commonly studied host-parasite systems. We summarize known host-parasite relationships in these three systems and propose testable hypotheses that could improve our understanding of links between host sociality and parasite-dynamics in bats.


id: cord-019068-6j42euvc
title: Life Cycle and Life History Strategies of Parasitic Crustacea
author: Williams, Ernest H.
date: 2019-07-05
txt: ./txt/cord-019068-6j42euvc.txt
cache: ./cache/cord-019068-6j42euvc.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7124122/
doi: 10.1007/978-3-030-17385-2_5
summary:
  Mating takes place soon Fig. 5.2 The generalised life cycle of an Ergasilus von Nordmann, 1832, species showing the freeliving naupliar and copepodid stages as well as the parasitic adult female. Cleaner shrimp similarly snip off the legs of small crustacean parasites to remove and eat them (Williams and Bunkley-Williams 1998b, unpublished data Many copepod parasites of invertebrates also have direct life cycles, but some have endoparasitic larvae and free-swimming adults, mesoparasitic larvae and ectoparasitic adults, and abbreviated or no larval stages. The free-living stages in the life cycles of ergasilids and many of the copepod species parasitising invertebrates suggest that they have more recently evolved a parasitic lifestyle. In parasitic copepods, the infective larva is, with rare exceptions, the first copepodid, and life cycles are direct, involving only a single host.

abstract:
  Different parasitic life strategies are described including four new life cycles: complex rebrooding, micro-male, mesoparasite and prey-predator transfer. Four new life cycle behaviours are named: nursery hiding, mid-moult stage, positive precursor (intraspecific antagonism) and negative precursor (ambush strategy). Further strategies discussed are opossum attack, double parasitism (doubling of the normal reproductive set), duplex arrangement (separated male-female pairs), simple rebrooding, and describing how displaced parasites and superinfections may partly elucidate life cycles. Proportional stunting masks life history effects of parasitism; cuckoo copepods are true parasites and not just associates; burrowing barnacles (acrothoracicans) are not parasites. Further findings based on life cycle information: branchiurans and pentastomes are possibly not related; firefly seed shrimp are not parasites; copepod pre-adult life cycle stages are common in the western pacific but rare in Caribbean; harpacticoids on vertebrates are not parasites; cuckoo copepods are true parasites; explained the importance of pennellid intermediate hosts. Crustacean parasite life cycles are largely unknown (1% of species). Most crustacean life cycles represent minor modifications from the ancestral free-living mode. Crustacean parasites have less complex and less modified life cycles than other major parasite groups. This limits their exploitation of, and effectiveness, in parasitism. However, these life cycles will be an advantage in Global Change. Most metazoan parasites will be eliminated while crustaceans (and nematodes) will inherit the new world of parasites.


id: cord-021552-6jbm869r
title: Relationship Between Humans and Their Viruses
author: HURST, CHRISTON J.
date: 2007-05-09
txt: ./txt/cord-021552-6jbm869r.txt
cache: ./cache/cord-021552-6jbm869r.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7150212/
doi: 10.1016/b978-012362675-2/50015-x
abstract: nan
summary:
  Viral replication ~ at the individual host level, the primary tissue and organ tropisms are toward the cervix, conjunctiva, pharynx, small intestine, and urethra; the secondary tissue and organ tropisms are toward the brain, kidney, lungs, and lymph nodes; at the host population level, these viruses generally are endemic and initially acquired at a very early age, with the infections very often asymptomatic in young children. ~ral replication ~ at the individual host level, primary tissue and organ tropisms are toward the small intestine; secondary tissue and organ tropisms are toward the liver; at the host population level, these tend to be epidemic within human populations; for the hepatitis E virus it seems that acquisition occurs from swine, with the result being epidemics (often very widespread) of human disease; some acquisition from animals may come from eating infected animals; subsequent transmission of all caliciviruses within human populations is by fecally contaminated waste and thus can be very widespread. Alternate hosts: One species of viral family Hepadnaviridae (hepatitis B virus) is known to infect humans, and it seems naturally limited to humans.


id: cord-026880-i45okohf
author: Hartigan, Ashlie
date: 2020-06-16
txt: ./txt/cord-026880-i45okohf.txt
cache: ./cache/cord-026880-i45okohf.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7296530/
doi: 10.1186/s12864-020-6705-y
summary:
  title: Transcriptome of Sphaerospora molnari (Cnidaria, Myxosporea) blood stages provides proteolytic arsenal as potential therapeutic targets against sphaerosporosis in common carp Myxozoans are parasitic cnidarians that are important pathogens to both wild and cultured fish populations and yet there are no drug targets specified for this group and limited proteolytic studies to examine activity or function of selected proteins [9, 10] . vulgaris isoforms contained a transmembrane domain and a high homology to DPPIVs rather than POPs. We then examined the expression of eight key proteases in blood stages compared to spore forming gill stages by qPCR and also in silico expression (TPM). The divergence in sequence identity from their host, their expression in both blood and gill stages and their similarity to proteases that have been successfully blocked in such assays are all good evidence that these could be the first drug targets for S.

title:
  Transcriptome of Sphaerospora molnari (Cnidaria, Myxosporea) blood stages provides proteolytic arsenal as potential therapeutic targets against sphaerosporosis in common carp

abstract:
  BACKGROUND: Parasites employ proteases to evade host immune systems, feed and replicate and are often the target of anti-parasite strategies to disrupt these interactions. Myxozoans are obligate cnidarian parasites, alternating between invertebrate and fish hosts. Their genes are highly divergent from other metazoans, and available genomic and transcriptomic datasets are limited. Some myxozoans are important aquaculture pathogens such as Sphaerospora molnari replicating in the blood of farmed carp before reaching the gills for sporogenesis and transmission. Proliferative stages cause a massive systemic lymphocyte response and the disruption of the gill epithelia by spore-forming stages leads to respiratory problems and mortalities. In the absence of a S. molnari genome, we utilized a de novo approach to assemble the first transcriptome of proliferative myxozoan stages to identify S. molnari proteases that are upregulated during the first stages of infection when the parasite multiplies massively, rather than in late spore-forming plasmodia. Furthermore, a subset of orthologs was used to characterize 3D structures and putative druggable targets. RESULTS: An assembled and host filtered transcriptome containing 9436 proteins, mapping to 29,560 contigs was mined for protease virulence factors and revealed that cysteine proteases were most common (38%), at a higher percentage than other myxozoans or cnidarians (25–30%). Two cathepsin Ls that were found upregulated in spore-forming stages with a presenilin like aspartic protease and a dipeptidyl peptidase. We also identified downregulated proteases in the spore-forming development when compared with proliferative stages including an astacin metallopeptidase and lipases (qPCR). In total, 235 transcripts were identified as putative proteases using a MEROPS database. In silico analysis of highly transcribed cathepsins revealed potential drug targets within this data set that should be prioritised for development. CONCLUSIONS: In silico surveys for proteins are essential in drug discovery and understanding host-parasite interactions in non-model systems. The present study of S. molnari’s protease arsenal reveals previously unknown proteases potentially used for host exploitation and immune evasion. The pioneering dataset serves as a model for myxozoan virulence research, which is of particular importance as myxozoan diseases have recently been shown to emerge and expand geographically, due to climate change.


id: cord-029032-s9geepsc
title: Parasite-Guest Infection Modeling: Social Science Applications
author: Vargas-García, Cesar
date: 2020-06-22
txt: ./txt/cord-029032-s9geepsc.txt
cache: ./cache/cord-029032-s9geepsc.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7354776/
doi: 10.1007/978-3-030-53956-6_55
summary:
  This theory states that natural selection maximizes the number of secondary infections resulting from infection of a susceptible host through free channels that do not involve direct contact between infected and susceptible hosts [7] . The proposed section reviews the classical and recent models that try to explain this phenomenon It has been suggested that infection channels between infected and susceptible hosts may provide an advantage, either by allowing parasites to evade the host''s immune response [10] , reducing antiviral drug activity [11] , or simply having a more efficient mode of infection. In the second section, a novel model of parasite-host interactions is proposed that accounts for transmission, both through free channels (not involving contact between infected and susceptible hosts), and through infections produced by contact between hosts. This shielding effect can be incorporated into the previous model, assuming the number of parasites released by the death of an infected host as a function of the infection rate [14] .

abstract:
  In this study we argue that parasite-host infections are a major research topic because of their implications for human health, agriculture and wildlife. The evolution of infection mechanisms is a research topic in areas such as virology and ecology. Mathematical modelling has been an essential tool to obtain a better systematic and quantitative understanding of the processes of parasitic infection that are difficult to discern through strictly experimental approaches. In this article we review recent attempts using mathematical models to discriminate and quantify these infection mechanisms. We also emphasize the challenges that these models could bring to new fields of study such as social sciences and economics.


id: cord-031937-qhlatg84
author: Verma, Anukriti
date: 2020-09-15
txt: ./txt/cord-031937-qhlatg84.txt
cache: ./cache/cord-031937-qhlatg84.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7492238/
doi: 10.1038/s41598-020-71674-8
summary:
  In-silico analysis involving text mining, metabolic network reconstruction, simulation, filtering, host-microbe interaction, docking and molecular mimicry studies results in robust drug target/s and biomarker/s for co-evolved IBD and ReA. The contributions of the microorganisms in the co-evolved IBD and ReA as part of the disease network was created through the interactive maps of the essential host interaction proteins (verified using literature survey) and the information processed through gene expression data analysis 64 . The pathways of the above host interacting proteins were found out using KEGG database that provides ontologies for proteins related to biological processes 67 www.nature.com/scientificreports/ Subsequently, the role of drugs or inhibitors used to suppress the effect of IBD and ReA such as indomethacin, prednisone, ciprofloxacin, sulfasalazine, azathioprine, methotrexate and hydroxychloroquine was scored in the disease network through their docking studies against the potential targets (both host as well microbial targets) as per published methodologies 68, 69 .

title:
  Elucidating potential molecular signatures through host-microbe interactions for reactive arthritis and inflammatory bowel disease using combinatorial approach

abstract:
  Reactive Arthritis (ReA), a rare seronegative inflammatory arthritis, lacks exquisite classification under rheumatic autoimmunity. ReA is solely established using differential clinical diagnosis of the patient cohorts, where pathogenic triggers linked to enteric and urogenital microorganisms e.g. Salmonella, Shigella, Yersinia, Campylobacter, Chlamydia have been reported. Inflammatory Bowel Disease (IBD), an idiopathic enteric disorder co-evolved and attuned to present gut microbiome dysbiosis, can be correlated to the genesis of enteropathic arthropathies like ReA. Gut microbes symbolically modulate immune system homeostasis and are elementary for varied disease patterns in autoimmune disorders. The gut-microbiota axis structured on the core host-microbe interactions execute an imperative role in discerning the etiopathogenesis of ReA and IBD. This study predicts the molecular signatures for ReA with co-evolved IBD through the enveloped host-microbe interactions and microbe-microbe ‘interspecies communication’, using synonymous gene expression data for selective microbes. We have utilized a combinatorial approach that have concomitant in-silico work-pipeline and experimental validation to corroborate the findings. In-silico analysis involving text mining, metabolic network reconstruction, simulation, filtering, host-microbe interaction, docking and molecular mimicry studies results in robust drug target/s and biomarker/s for co-evolved IBD and ReA. Cross validation of the target/s or biomarker/s was done by targeted gene expression analysis following a non-probabilistic convenience sampling. Studies were performed to substantiate the host-microbe disease network consisting of protein-marker-symptom/disease-pathway-drug associations resulting in possible identification of vital drug targets, biomarkers, pathways and inhibitors for IBD and ReA. Our study identified Na((+))/H((+)) anti-porter (NHAA) and Kynureninase (KYNU) to be robust early and essential host-microbe interacting targets for IBD co-evolved ReA. Other vital host-microbe interacting genes, proteins, pathways and drugs include Adenosine Deaminase (ADA), Superoxide Dismutase 2 (SOD2), Catalase (CAT), Angiotensin I Converting Enzyme (ACE), carbon metabolism (folate biosynthesis) and methotrexate. These can serve as potential prognostic/theranostic biomarkers and signatures that can be extrapolated to stratify ReA and related autoimmunity patient cohorts for further pilot studies.


id: cord-048325-pk7pnmlo
title: An object simulation model for modeling hypothetical disease epidemics – EpiFlex
author: Hanley, Brian
date: 2006-08-23
txt: ./txt/cord-048325-pk7pnmlo.txt
cache: ./cache/cord-048325-pk7pnmlo.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1570461/
doi: 10.1186/1742-4682-3-32
summary:
  RESULTS: EpiFlex indicates three phenomena of interest for public health: (1) R(0 )is variable, and the smaller the population, the larger the infected fraction within that population will be; (2) significant compression/synchronization between cities by a factor of roughly 2 occurs between the early incubation phase of a multi-city epidemic and the major manifestation phase; (3) if better true morbidity data were available, more asymptomatic hosts would be seen to spread disease than we currently believe is the case for influenza. EpiFlex uses a dynamic network to model the interactions between hosts at a particular location based on the skew provided and the demographic segments movement cycles. The EpiFlex system iterates through all areas in a model and allocates hosts, putting them in their initial locations, per the movement definitions for the demographic group.

abstract:
  BACKGROUND: EpiFlex is a flexible, easy to use computer model for a single computer, intended to be operated by one user who need not be an expert. Its purpose is to study in-silico the epidemic behavior of a wide variety of diseases, both known and theoretical, by simulating their spread at the level of individuals contracting and infecting others. To understand the system fully, this paper must be read together in conjunction with study of the software and its results. EpiFlex is evaluated using results from modeling influenza A epidemics and comparing them with a variety of field data sources and other types of modeling. EpiFlex is an object-oriented Monte Carlo system, allocating entities to correspond to individuals, disease vectors, diseases, and the locations that hosts may inhabit. EpiFlex defines eight different contact types available for a disease. Contacts occur inside locations within the model. Populations are composed of demographic groups, each of which has a cycle of movement between locations. Within locations, superspreading is defined by skewing of contact distributions. RESULTS: EpiFlex indicates three phenomena of interest for public health: (1) R(0 )is variable, and the smaller the population, the larger the infected fraction within that population will be; (2) significant compression/synchronization between cities by a factor of roughly 2 occurs between the early incubation phase of a multi-city epidemic and the major manifestation phase; (3) if better true morbidity data were available, more asymptomatic hosts would be seen to spread disease than we currently believe is the case for influenza. These results suggest that field research to study such phenomena, while expensive, should be worthwhile. CONCLUSION: Since EpiFlex shows all stages of disease progression, detailed insight into the progress of epidemics is possible. EpiFlex shows the characteristic multimodality and apparently random variation characteristic of real world data, but does so as an emergent property of a carefully constructed model of disease dynamics and is not simply a stochastic system. EpiFlex can provide a better understanding of infectious diseases and strategies for response.


id: cord-102383-m5ahicqb
title: Energy dynamics for systemic configurations of virus-host co-evolution
author: Romano, Alessandra
date: 2020-05-15
txt: ./txt/cord-102383-m5ahicqb.txt
cache: ./cache/cord-102383-m5ahicqb.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1101/2020.05.13.092866
doi: 10.1101/2020.05.13.092866
summary:
  A systems-thinking representation, based on stock-flow diagramming of virus-host interaction at the cellular level, is used here for the first time to simulate the system energy dynamics. A systems-thinking representation, based on stock-flow diagramming of virus-host interaction at the cellular level, is used here for the first time to simulate the system energy dynamics. A systems-thinking representation, based on stock-flow diagramming of virus-host interaction at the cellular level, is used here for the first time to simulate the system energy dynamics. Viral load and early addressing (in the first two days from infection) of leverage points are the most effective strategies on stock dynamics to minimize virion assembly and preserve host-cell bioenergetics. Viral load and early addressing (in the first two days from infection) of leverage points are the most effective strategies on stock dynamics to minimize virion assembly and preserve host-cell bioenergetics.

abstract:
  Virus cause multiple outbreaks, for which comprehensive tailored therapeutic strategies are still missing. Virus and host cell dynamics are strictly connected, and convey in virion assembly to ensure virus spread in the body. Study of the systemic behavior of virus-host interaction at the single-cell level is a scientific challenge, considering the difficulties of using experimental approaches and the limited knowledge of the behavior of emerging novel virus as a collectivity. This work focuses on positive-sense, single-stranded RNA viruses, like human coronaviruses, in their virus-individual host interaction, studying the changes induced in the host cell bioenergetics. A systems-thinking representation, based on stock-flow diagramming of virus-host interaction at the cellular level, is used here for the first time to simulate the system energy dynamics. We found that reducing the energy flow which fuels virion assembly is the most affordable strategy to limit the virus spread, but its efficacy is mitigated by the contemporary inhibition of other flows relevant for the system. Summary Positive-single-strand ribonucleic acid ((+)ssRNA) viruses can cause multiple outbreaks, for which comprehensive tailored therapeutic strategies are still missing. Virus and host cell dynamics are strictly connected, generating a complex dynamics that conveys in virion assembly to ensure virus spread in the body. This work focuses on (+)ssRNA viruses in their virus-individual host interaction, studying the changes induced in the host cell bioenergetics. A systems-thinking representation, based on stock-flow diagramming of virus-host interaction at the cellular level, is used here for the first time to simulate the energy dynamics of the system. By means of a computational simulator based on the systemic diagramming, we identifid host protein recycling and folded-protein synthesis as possible new leverage points. These also address different strategies depending on time setting of the therapeutic procedures. Reducing the energy flow which fuels virion assembly is addressed as the most affordable strategy to limit the virus spread, but its efficacy is mitigated by the contemporary inhibition of other flows relevant for the system. Counterintuitively, targeting RNA replication or virion budding does not give rise to relevant systemic effects, and can possibly contribute to further virus spread. The tested combinations of multiple systemic targets are less efficient in minimizing the stock of virions than targeting only the virion assembly process, due to the systemic configuration and its evolution overtime. Viral load and early addressing (in the first two days from infection) of leverage points are the most effective strategies on stock dynamics to minimize virion assembly and preserve host-cell bioenergetics. As a whole, our work points out the need for a systemic approach to design effective therapeutic strategies that should take in account the dynamic evolution of the system.


id: cord-104317-t30dg6oj
author: Parker, Michael T.
date: 2016-09-30
txt: ./txt/cord-104317-t30dg6oj.txt
cache: ./cache/cord-104317-t30dg6oj.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5045143/
doi: nan
summary:
  However, the obvious importance of viruses in the composition of all biomes has not (yet) been met with an appropriate fervor for the characterization of the viral REVIEW Recent advances in sequencing technologies have opened the door for the classification of the human virome. The discovery of intimate interactions of viruses with humans, like the role of endogenous retrovirus (ERV †) syncytins in placentation [27] , are categorically dissimilar to the classical view of viruses only as parasites and brings to issue how scientists are approaching the study of the virome. The application of this scaffold will not only deepen the understanding of known virus-host interactions in the ecological context of the virome, but will also identify logical next steps and gaps in current knowledge that are tantalizing areas for future exploration. Additionally, further characterization of the human virome is likely to uncover more viruses that persistently infect humans [31] , and such discoveries could pave the way for the treatment of diseases of currently unknown etiology.

title:
  An Ecological Framework of the Human Virome Provides Classification of Current Knowledge and Identifies Areas of Forthcoming Discovery

abstract:
  Recent advances in sequencing technologies have opened the door for the classification of the human virome. While taxonomic classification can be applied to the viruses identified in such studies, this gives no information as to the type of interaction the virus has with the host. As follow-up studies are performed to address these questions, the description of these virus-host interactions would be greatly enriched by applying a standard set of definitions that typify them. This paper describes a framework with which all members of the human virome can be classified based on principles of ecology. The scaffold not only enables categorization of the human virome, but can also inform research aimed at identifying novel virus-host interactions.


id: cord-199630-2lmwnfda
author: Ray, Sumanta
date: 2020-07-05
txt: ./txt/cord-199630-2lmwnfda.txt
cache: ./cache/cord-199630-2lmwnfda.txt
extension: .txt
mime: text/plain
url: https://arxiv.org/pdf/2007.02338v1.pdf
doi: nan
summary:
  Therefore, host-(1) We link existing high-quality, long-term curated and refined, large scale drug/protein -protein interaction data with (2) molecular interaction data on SARS-CoV-2 itself, raised only a handful of weeks ago, (3) exploit the resulting overarching network using most advanced, AI boosted techniques (4) for repurposing drugs in the fight against SARS-CoV-2 (5) in the frame of HDT based strategies. As for (3)-(5), we will highlight interactions between SARS-Cov-2-host protein and human proteins important for the virus to persist using most advanced deep learning techniques that cater to exploiting network data. As per our simulation study, a large fraction, if not the vast majority of the predictions establish true, hence actionable interactions between drugs on the one hand and SARS-CoV-2 associated human proteins (hence of use in HDT) on the other hand.

title:
  Predicting potential drug targets and repurposable drugs for COVID-19 via a deep generative model for graphs

abstract:
  Coronavirus Disease 2019 (COVID-19) has been creating a worldwide pandemic situation. Repurposing drugs, already shown to be free of harmful side effects, for the treatment of COVID-19 patients is an important option in launching novel therapeutic strategies. Therefore, reliable molecule interaction data are a crucial basis, where drug-/protein-protein interaction networks establish invaluable, year-long carefully curated data resources. However, these resources have not yet been systematically exploited using high-performance artificial intelligence approaches. Here, we combine three networks, two of which are year-long curated, and one of which, on SARS-CoV-2-human host-virus protein interactions, was published only most recently (30th of April 2020), raising a novel network that puts drugs, human and virus proteins into mutual context. We apply Variational Graph AutoEncoders (VGAEs), representing most advanced deep learning based methodology for the analysis of data that are subject to network constraints. Reliable simulations confirm that we operate at utmost accuracy in terms of predicting missing links. We then predict hitherto unknown links between drugs and human proteins against which virus proteins preferably bind. The corresponding therapeutic agents present splendid starting points for exploring novel host-directed therapy (HDT) options.


id: cord-255181-du6rqc6i
author: Louz, Derrick
date: 2005-06-29
txt: ./txt/cord-255181-du6rqc6i.txt
cache: ./cache/cord-255181-du6rqc6i.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/15986492/
doi: 10.1002/jgm.794
summary:
  This review addresses a number of potential risk factors and their implications for activities with viral vectors from the perspective of cross‐species transfer of viruses in nature, with emphasis on the occurrence of host‐range mutants resulting from either cell culture or tropism engineering. The HIV virus and contemporary human influenza viruses are prominent examples of viruses that have crossed the species barrier and established themselves permanently in the human population without further dependence on the presence of the original animal host reservoir. The emergence of HIV exemplifies how multiple independent cross-species transmissions of simian viruses that are not associated with disease in their natural hosts eventually resulted in the establishment of two types of HIV in the human population. The following examples demonstrate that upon persistent infection and passage in cell culture, cross-species transmissibility may be promoted by selection of virus variants with an altered host range. Adaptation in cell culture may result in changes in receptor specificity and tropism, and leads to the emergence of host-range mutant viruses.

title:
  Cross‐species transfer of viruses: implications for the use of viral vectors in biomedical research, gene therapy and as live‐virus vaccines

abstract:
  Summary All living organisms are continuously exposed to a plethora of viruses. In general, viruses tend to be restricted to the natural host species which they infect. From time to time viruses cross the host‐range barrier expanding their host range. However, in very rare cases cross‐species transfer is followed by the establishment and persistence of a virus in the new host species, which may result in disease. Recent examples of viruses that have crossed the species barrier from animal reservoirs to humans are hantavirus, haemorrhagic fever viruses, arboviruses, Nipah and Hendra viruses, avian influenza virus (AI), monkeypox virus, and the SARS‐associated coronavirus (SARS‐CoV). The opportunities for cross‐species transfer of mammalian viruses have increased in recent years due to increased contact between humans and animal reservoirs. However, it is difficult to predict when such events will take place since the viral adaptation that is needed to accomplish this is multifactorial and stochastic. Against this background the intensified use of viruses and their genetically modified variants as viral gene transfer vectors for biomedical research, experimental gene therapy and for live‐vector vaccines is a cause for concern. This review addresses a number of potential risk factors and their implications for activities with viral vectors from the perspective of cross‐species transfer of viruses in nature, with emphasis on the occurrence of host‐range mutants resulting from either cell culture or tropism engineering. The issues are raised with the intention to assist in risk assessments for activities with vector viruses. Copyright © 2005 John Wiley & Sons, Ltd.


id: cord-259505-7hiss0j3
title: Proteomic analysis of purified coronavirus infectious bronchitis virus particles
author: Kong, Qingming
date: 2010-06-09
txt: ./txt/cord-259505-7hiss0j3.txt
cache: ./cache/cord-259505-7hiss0j3.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/20534109/
doi: 10.1186/1477-5956-8-29
summary:
  It is an important prerequisite for the functional studies to know the protein composition of the purified viral particles, as it allows the analysis of specific proteins and their roles during the virus life cycle, resulting in better understanding of the infection process and the pathogenesis of viruses. To date, there have been no reports about TENP associated with virus, but it''s an enriched and abundant protein identified in purified infectious bronchitis particles which suggests to us that it may be a requisite host protein in IBV life cycles. The present study 1) provides the first proteomic analysis of infectious bronchitis particles, 2) establishes the most comprehensive proteomic index of IBV and 3) shows that most of the virion incorporated host proteins have central roles in virus life cycle.

abstract:
  BACKGROUND: Infectious bronchitis virus (IBV) is the coronavirus of domestic chickens causing major economic losses to the poultry industry. Because of the complexity of the IBV life cycle and the small number of viral structural proteins, important virus-host relationships likely remain to be discovered. Toward this goal, we performed two-dimensional gel electrophoresis fractionation coupled to mass spectrometry identification approaches to perform a comprehensive proteomic analysis of purified IBV particles. RESULTS: Apart from the virus-encoded structural proteins, we detected 60 host proteins in the purified virions which can be grouped into several functional categories including intracellular trafficking proteins (20%), molecular chaperone (18%), macromolcular biosynthesis proteins (17%), cytoskeletal proteins (15%), signal transport proteins (15%), protein degradation (8%), chromosome associated proteins (2%), ribosomal proteins (2%), and other function proteins (3%). Interestingly, 21 of the total host proteins have not been reported to be present in virions of other virus families, such as major vault protein, TENP protein, ovalbumin, and scavenger receptor protein. Following identification of the host proteins by proteomic methods, the presence of 4 proteins in the purified IBV preparation was verified by western blotting and immunogold labeling detection. CONCLUSIONS: The results present the first standard proteomic profile of IBV and may facilitate the understanding of the pathogenic mechanisms.


id: cord-261466-b9r4cyp7
title: What is the importance of zoonotic trichomonads for human health?
author: Maritz, Julia M.
date: 2014-06-18
txt: ./txt/cord-261466-b9r4cyp7.txt
cache: ./cache/cord-261466-b9r4cyp7.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S1471492214000919
doi: 10.1016/j.pt.2014.05.005
summary:
  Four species of trichomonad are considered human parasites: Trichomonas vaginalis (found in the urogenital tract) [6] , Trichomonas tenax (localized to the oral cavity) [7] , and Pentatrichomonas hominis and Dientamoeba fragilis (located in the digestive tract) [8, 9] . In addition, several trichomonad species are of veterinary importance, such as the avian pathogens Trichomonas gallinae, Tetratrichomonas gallinarum, and Histomonas meleagridis [16] [17] [18] [19] , and Tritrichomonas foetus, the causative agent of a venereal disease in cattle [20] . Thus, the presence of an increasing number of distinct trichomonads in a broader range of clinical samples from patients with diverse diseases, such as AIDS, rheumatoid arthritis, prostate cancer, pulmonary infections (empyema and pneumonia in addition to PcP and ARDS), and digestive conditions such as diarrhea and IBS [33] [34] [35] , is becoming increasingly apparent.

abstract:
  Trichomonads are common parasites of many vertebrate and invertebrate species, with four species classically recognized as human parasites: Dientamoeba fragilis, Pentatrichomonas hominis, Trichomonas vaginalis, and Trichomonas tenax. The latter two species are considered human-specific; by contrast, D. fragilis and P. hominis have been isolated from domestic and farm mammals, demonstrating a wide host range and potential zoonotic origin. Several new studies have highlighted the zoonotic dimension of trichomonads. First, species typically known to infect birds and domestic mammals have been identified in human clinical samples. Second, several phylogenetic analyses have identified animal-derived trichomonads as close sister taxa of the two human-specific species. It is our opinion, therefore, that these observations prompt further investigation into the importance of zoonotic trichomonads for human health.


id: cord-262434-q4tk96tq
title: Poxviruses in Bats … so What?
author: Baker, Kate S.
date: 2014-04-03
txt: ./txt/cord-262434-q4tk96tq.txt
cache: ./cache/cord-262434-q4tk96tq.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3390/v6041564
doi: 10.3390/v6041564
summary:
  Finally, we speculate on the possible consequences and potential research avenues opened following this marrying of a pathogen of great historical and contemporary importance with an ancient host that has an apparently peculiar relationship with viruses; a fascinating and likely fruitful meeting whose study will be facilitated by recent technological advances and a heightened interest in bat virology. Similarly, testing the in vitro host range of isolated viruses such as Eptesipox virus would help inform whether human and further animal cell lines are permissive for infection (i.e., that they contain the necessary host factors to support infection and do not contain antiviral components that restrict infection). Further field (in situ), in vitro and in silico studies could elucidate the possible coevolution, cross species infections and mechanisms of host range restriction of bat poxviruses, the implications of which are relevant for bat ecologists, virologists and emerging infectious disease specialists (including those with a specific interest in bats) alike.

abstract:
  Poxviruses are important pathogens of man and numerous domestic and wild animal species. Cross species (including zoonotic) poxvirus infections can have drastic consequences for the recipient host. Bats are a diverse order of mammals known to carry lethal viral zoonoses such as Rabies, Hendra, Nipah, and SARS. Consequent targeted research is revealing bats to be infected with a rich diversity of novel viruses. Poxviruses were recently identified in bats and the settings in which they were found were dramatically different. Here, we review the natural history of poxviruses in bats and highlight the relationship of the viruses to each other and their context in the Poxviridae family. In addition to considering the zoonotic potential of these viruses, we reflect on the broader implications of these findings. Specifically, the potential to explore and exploit this newfound relationship to study coevolution and cross species transmission together with fundamental aspects of poxvirus host tropism as well as bat virology and immunology.


id: cord-262585-5vjqrnwh
title: Resources to Discover and Use Short Linear Motifs in Viral Proteins
author: Hraber, Peter
date: 2019-08-16
txt: ./txt/cord-262585-5vjqrnwh.txt
cache: ./cache/cord-262585-5vjqrnwh.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/31427097/
doi: 10.1016/j.tibtech.2019.07.004
summary:
  Viral proteins evade host immune function by molecular mimicry, often achieved by short linear motifs (SLiMs) of three to ten consecutive amino acids (AAs). Molecular mimicry varies over a continuum, from one extreme that includes sequence and structural similarity (i.e., orthologs) of entire proteins, to another extreme of chemical similarity at only a few localized sites, as is the case for short linear motifs (SLiMs). Viral SLiMs are potentially useful in synthetic biology, to provide a toolkit for new functions, for example, to modulate immune responses or to complement and interact with newly developed adjuvants in a synergistic manner [9] . Research efforts to develop broad-spectrum antiviral compounds or design broadly cross-protective vaccine immunogens benefit directly from knowledge of gene products, protein functions, and motifs involved with viral immune interference. SLiMs are useful in synthetic biology, where minor edits can alter target specificity, modulate persistence, reprogram interactions with cell-signaling domains, and alter protein function in myriad other ways.

abstract:
  Viral proteins evade host immune function by molecular mimicry, often achieved by short linear motifs (SLiMs) of three to ten consecutive amino acids (AAs). Motif mimicry tolerates mutations, evolves quickly to modify interactions with the host, and enables modular interactions with protein complexes. Host cells cannot easily coordinate changes to conserved motif recognition and binding interfaces under selective pressure to maintain critical signaling pathways. SLiMs offer potential for use in synthetic biology, such as better immunogens and therapies, but may also present biosecurity challenges. We survey viral uses of SLiMs to mimic host proteins, and information resources available for motif discovery. As the number of examples continues to grow, knowledge management tools are essential to help organize and compare new findings.


id: cord-262682-gsvswr7v
title: Segmented Filamentous Bacteria – Metabolism Meets Immunity
author: Hedblom, Grant A.
date: 2018-08-24
txt: ./txt/cord-262682-gsvswr7v.txt
cache: ./cache/cord-262682-gsvswr7v.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/30197636/
doi: 10.3389/fmicb.2018.01991
summary:
  SFB have recently garnered attention due to their role in promoting adaptive and innate immunity in mice and rats through the differentiation and maturation of Th17 cells in the intestinal tract and production of immunoglobulin A (IgA). Although the role of SFB to induce antigen-specific Th17 cells in poultry is unknown, they may play an important role in modulating the immune response in the intestinal tract to promote resistance against some infectious diseases and promote food-safety. Many vertebrate intestines (such as mice, rats, chickens, humans, and turkeys) harbor commensal organisms named segmented filamentous bacteria (SFB) that bind specifically to the host intestinal epithelium. The role of SFB in Th17 cell production was initially demonstrated when mice were inoculated with mouse, rat, and human microbiota containing bacterial spores similar to that of the genus Clostridium. Colonization and distribution of segmented filamentous bacteria (SFB) in chicken gastrointestinal tract and their relationship with host immunity

abstract:
  Segmented filamentous bacteria (SFB) are a group of host-adapted, commensal organisms that attach to the ileal epithelium of vertebrate and invertebrate hosts. A genetic relative of the genus Clostridium, these morphologically unique bacteria display a replication and differentiation lifecycle initiated by epithelial tissue binding and filamentation. SFB intimately bind to the surface of absorptive intestinal epithelium without inducing an inflammatory response. Rather, their presence impacts the generation of innate and differentiation of acquired immunity, which impact the clearance of extracellular bacterial or fungal pathogens in the gastrointestinal and respiratory tracts. SFB have recently garnered attention due to their role in promoting adaptive and innate immunity in mice and rats through the differentiation and maturation of Th17 cells in the intestinal tract and production of immunoglobulin A (IgA). SFB are the first commensal bacteria identified that impact the maturation and development of Th17 cells in mice. Recently, microbiome studies have revealed the presence of Candidatus Arthromitus (occasionally designated as Candidatus Savagella), a proposed candidate species of SFB, in higher proportions in higher-performing flocks as compared to matched lower-performing flocks, suggesting that SFB may serve to establish a healthy gut and protect commercial turkeys from pathogens resulting in morbidity and decreased performance. In this review we seek to describe the life cycle, host specificity, and genetic capabilities of SFB, such as bacterial metabolism, and how these factors influence the host immunity and microbiome. Although the role of SFB to induce antigen-specific Th17 cells in poultry is unknown, they may play an important role in modulating the immune response in the intestinal tract to promote resistance against some infectious diseases and promote food-safety. This review demonstrates the importance of studying and further characterizing commensal, host-specific bacteria in food-producing animals and their importance to animal health.


id: cord-263312-x7f0hn7f
title: Drosophila melanogaster: a first step and a stepping-stone to anti-infectives
author: Tzelepis, Ilias
date: 2013-08-28
txt: ./txt/cord-263312-x7f0hn7f.txt
cache: ./cache/cord-263312-x7f0hn7f.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.coph.2013.08.003
doi: 10.1016/j.coph.2013.08.003
summary:
  Drug screening in Drosophila offers to fill the gap between in vitro and mammalian model host testing by eliminating compounds that are toxic or have reduced bioavailability and by identifying others that may boost innate host defence or selectively reduce microbial virulence in a whole-organism setting. Drug screening in Drosophila offers to fill the gap between in vitro and mammalian model host testing by eliminating compounds that are toxic or have reduced bioavailability and by identifying others that may boost innate host defence or selectively reduce microbial virulence in a whole-organism setting. Flies have significant similarities with humans enabling a facile and cost effective assessment of anti-infective drugs during the interaction of microbes with a host. Human disease models in Drosophila melanogaster and the role of the fly in therapeutic drug discovery Drosophila melanogaster as a model host for studying Pseudomonas aeruginosa infection

abstract:
  Following an expansion in the antibiotic drug discovery in the previous century, we now face a bottleneck in the production of new anti-infective drugs. Traditionally, chemical libraries are screened either using in vitro culture systems or in silico to identify and chemically modify small molecules with antimicrobial properties. Nevertheless, almost all compounds passing through in vitro screening fail to pass preclinical trials. Drug screening in Drosophila offers to fill the gap between in vitro and mammalian model host testing by eliminating compounds that are toxic or have reduced bioavailability and by identifying others that may boost innate host defence or selectively reduce microbial virulence in a whole-organism setting. Such alternative screening methods in Drosophila, while low-throughput, may reduce the cost and increase the success rate of preclinical trials.


id: cord-264532-xfb94lq8
title: Invasion thresholds and the evolution of nonequilibrium virulence
author: Bull, James J
date: 2008-01-09
txt: ./txt/cord-264532-xfb94lq8.txt
cache: ./cache/cord-264532-xfb94lq8.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/25567500/
doi: 10.1111/j.1752-4571.2007.00003.x
summary:
  Evolution following invasion may be slow to attain the optimum Following Day and Proulx (2004) , if the invading parasite persists and becomes established, it is expected that virulence and transmission will begin to evolve toward values that improve parasite fitness. Yet, the approach to optimum virulence may be slow for a few reasons: (i) the optimum may be changing (Lenski and May 1994) , (ii) virulence evolution will be influenced by the genetic covariance or mutational properties between virulence and transmission (Day and Gandon 2006) , and Conditions for the invasion of a host population of density S* by a parasite with parameters (d, b) are S* > d/b, where d is virulence and b is the transmission rate. Likewise, if hosts merely die from the infection and do not recover (and are not resistant), then the invasion threshold model cannot possibly apply after dynamical equilibrium has been reached, because there is no reservoir of immune or resistant hosts to be exploited by a mutant parasite.

abstract:
  The enterprise of virulence management attempts to predict how social practices and other factors affect the evolution of parasite virulence. These predictions are often based on parasite optima or evolutionary equilibria derived from models of host-parasite dynamics. Yet even when such models accurately capture the parasite optima, newly invading parasites will typically not be at their optima. Here we show that parasite invasion of a host population can occur despite highly nonoptimal virulence. Fitness improvements soon after invasion may proceed through many steps with wide changes in virulence, because fitness depends on transmission as well as virulence, and transmission improvements can overwhelm nonoptimal virulence. This process is highly sensitive to mutation supply and the strength of selection. Importantly, the same invasion principle applies to the evolution of established parasites, whenever mutants arise that overcome host immunity/resistance. A host population may consequently experience repeated invasions of new parasite variants and possible large shifts in virulence as it evolves in an arms race with the parasite. An experimental study of phage lysis time and examples of mammalian viruses matching some of these characteristics are reviewed.


id: cord-264884-ydkigome
title: The Widespread Evolutionary Significance of Viruses
author: Villarreal, Luis P.
date: 2008-07-05
txt: ./txt/cord-264884-ydkigome.txt
cache: ./cache/cord-264884-ydkigome.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/B9780123741530000217
doi: 10.1016/b978-0-12-374153-0.00021-7
summary:
  For example, common structural motifs from phage to eukaryotic DNA viruses (T4 and herpesvirus) suggest very ancient links in virus evolution that span all domains of life (see below). On an evolutionary time-scale, the majority of viral lineages tend to exist as species-specifi c persistent (aka temperate, latent, and chronic) infections in which individual hosts will be colonized by mostly silent (asymptomatic) viruses for the duration of their life . It has distinct genetic, fi tness, and evolutionary characteristics that require intimate, host (tissue)-specifi c viral strategies and precise gene functions to attain stable maintenance in the presence of immunity and to allow biologically controlled reactivation. Thus, the phycodnaviruses appear to represent a basal but diverse viral lineage that has both acute and persistent lifestyle and have some clear relationships to most large eukaryotic DNA viruses and many phage.

abstract:
  In the last 30 years, the study of virus evolution has undergone a transformation. Originally concerned with disease and its emergence, virus evolution had not been well integrated into the general study of evolution. This chapter reviews the developments that have brought us to this new appreciation for the general significance of virus evolution to all life. We now know that viruses numerically dominate all habitats of life, especially the oceans. Theoretical developments in the 1970s regarding quasispecies, error rates, and error thresholds have yielded many practical insights into virus–host dynamics. The human diseases of HIV-1 and hepatitis C virus cannot be understood without this evolutionary framework. Yet recent developments with poliovirus demonstrate that viral fitness can be the result of a consortia, not one fittest type, a basic Darwinian concept in evolutionary biology. Darwinian principles do apply to viruses, such as with Fisher population genetics, but other features, such as reticulated and quasispecies-based evolution distinguish virus evolution from classical studies. The available phylogenetic tools have greatly aided our analysis of virus evolution, but these methods struggle to characterize the role of virus populations. Missing from many of these considerations has been the major role played by persisting viruses in stable virus evolution and disease emergence. In many cases, extreme stability is seen with persisting RNA viruses. Indeed, examples are known in which it is the persistently infected host that has better survival. We have also recently come to appreciate the vast diversity of phage (DNA viruses) of prokaryotes as a system that evolves by genetic exchanges across vast populations (Chapter 10). This has been proposed to be the “big bang” of biological evolution. In the large DNA viruses of aquatic microbes we see surprisingly large, complex and diverse viruses. With both prokaryotic and eukaryotic DNA viruses, recombination is the main engine of virus evolution, and virus host co-evolution is common, although not uniform. Viral emergence appears to be an unending phenomenon and we can currently witness a selective sweep by retroviruses that infect and become endogenized in koala bears.


id: cord-269505-7g8lio9l
title: Impacts of biodiversity on the emergence and transmission of infectious diseases
author: Keesing, Felicia
date: 2010-12-01
txt: ./txt/cord-269505-7g8lio9l.txt
cache: ./cache/cord-269505-7g8lio9l.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/21124449/
doi: 10.1038/nature09575
summary:
  For hantavirus pulmonary syndrome, a directly transmitted zoonotic disease, correlational and experimental studies have shown that a lower diversity of small mammals increases the prevalence of hantaviruses in their hosts, thereby increasing risk to humans (Box 2). Diversity has a similar effect for plant diseases, with species losses increasing the transmission of two fungal rust pathogens that infect perennial rye grass and other plant species 10 . This is because field studies like those on West Nile virus, hantaviruses and rye grass have typically not controlled for changes in host density that can result from changes in ''species richness'' (the number of species present in a community, which is a measure of taxonomic diversity). In sum, reducing biodiversity can increase disease transmission when the lost species are either not hosts for the pathogen or are suboptimal ones. In several case studies, the species most likely to be lost from ecological communities as diversity declines are those most likely to reduce pathogen transmission.

abstract:
  Current unprecedented declines in biodiversity reduce the ability of ecological communities to provide many fundamental ecosystem services. Here we evaluate evidence that reduced biodiversity affects the transmission of infectious diseases of humans, other animals and plants. In principle, loss of biodiversity could either increase or decrease disease transmission. However, mounting evidence indicates that biodiversity loss frequently increases disease transmission. In contrast, areas of naturally high biodiversity may serve as a source pool for new pathogens. Overall, despite many remaining questions, current evidence indicates that preserving intact ecosystems and their endemic biodiversity should generally reduce the prevalence of infectious diseases. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nature09575) contains supplementary material, which is available to authorized users.


id: cord-269975-1ebmq7t8
title: Combating biothreat pathogens: ongoing efforts for countermeasure development and unique challenges
author: Duplantier, Allen J.
date: 2020-05-27
url: https://api.elsevier.com/content/article/pii/B9780128184806000072
doi: 10.1016/b978-0-12-818480-6.00007-2
abstract:
  Research to discover and develop antibacterial and antiviral drugs with potent activity against pathogens of biothreat concern presents unique methodological and process-driven challenges. Herein, we review laboratory approaches for finding new antibodies, antibiotics, and antiviral molecules for pathogens of biothreat concern. Using high-throughput screening techniques, molecules that directly inhibit a pathogen’s entry, replication, or growth can be identified. Alternatively, molecules that target host proteins can be interesting targets for development when countering biothreat pathogens, due to the modulation of the host immune response or targeting proteins that interfere with the pathways required by the pathogen for replication. Monoclonal and cocktail antibody therapies approved by the Food and Drug Administration for countering anthrax and under development for treatment of Ebola virus infection are discussed. A comprehensive tabular review of current in vitro, in vivo, pharmacokinetic and efficacy datasets has been presented for biothreat pathogens of greatest concern. Finally, clinical trials and animal rule or traditional drug approval pathways are also reviewed. Opinions; interpretations; conclusions; and recommendations are those of the authors and are not necessarily endorsed by the US Army.


id: cord-270604-u62437dh
title: A SIMPLE MODEL EXPLAINS THE DYNAMICS OF PREFERENTIAL HOST SWITCHING AMONG MAMMAL RNA VIRUSES
author: Cuthill, Jennifer Hoyal
date: 2013-02-19
txt: ./txt/cord-270604-u62437dh.txt
cache: ./cache/cord-270604-u62437dh.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/23550750/
doi: 10.1111/evo.12064
summary:
  We present an empirical test of two theoretical models of preferential host switching, using observed phylogenetic distributions of host species for RNA viruses of three mammal orders (primates, carnivores, and ungulates). To overcome the above complications, this study takes an alternative approach, and reconstructs the dynamics of preferential host switching among 38 recorded "multihost" RNA viruses of mammals, on phylogenies of their primate, carnivore, and ungulate hosts. To achieve this, approximate Bayesian computation (ABC) is used to test the fit of the two models of preferential host switching to the observed distributions of multihost RNA viruses on the phylogenies of their mammal hosts (primates, carnivores, and terrestrial ungulates). This indicates that ABC model selection was effective with each of the three sample sizes used for calculation of the HSD summary statistics (which corresponded to the number of observed host-virus associations, of 22 for primates, 12 for carnivores, and 4 for ungulates).

abstract:
  A growing number of studies support a tendency toward preferential host switching, by parasites and pathogens, over relatively short phylogenetic distances. This suggests that a host switch is more probable if a potential host is closely related to the original host than if it is a more distant relative. However, despite its importance for the health of humans, livestock, and wildlife, the detailed dynamics of preferential host switching have, so far, been little studied. We present an empirical test of two theoretical models of preferential host switching, using observed phylogenetic distributions of host species for RNA viruses of three mammal orders (primates, carnivores, and ungulates). The analysis focuses on multihost RNA virus species, because their presence on multiple hosts and their estimated ages of origin indicate recent host switching. Approximate Bayesian computation was used to compare observed phylogenetic distances between hosts with those simulated under the theoretical models. The results support a decreasing sigmoidal model of preferential host switching, with a strong effect from increasing phylogenetic distance, on all three studied host phylogenies. This suggests that the dynamics of host switching are fundamentally similar for RNA viruses of different mammal orders and, potentially, a wider range of coevolutionary systems.


id: cord-270803-jtv5jmkn
author: Wang, Lin-Fa
date: 2011-11-09
txt: ./txt/cord-270803-jtv5jmkn.txt
cache: ./cache/cord-270803-jtv5jmkn.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S1879625711001325
doi: 10.1016/j.coviro.2011.10.013
summary:
  This has been due to a combination of factors including the emergence of highly virulent zoonotic pathogens, such as Hendra, Nipah, SARS and Ebola viruses, and the high rate of detection of a large number of previously unknown viral sequences in bat specimens. This has been due to a combination of factors including the emergence of highly virulent zoonotic pathogens, such as Hendra, Nipah, SARS and Ebola viruses, and the high rate of detection of a large number of previously unknown viral sequences in bat specimens. Bats (order Chiroptera), one of the most abundant, diverse and geographically dispersed vertebrates on earth, have recently been shown to be reservoir hosts of a number of emerging viruses responsible for severe disease outbreaks in humans and livestock [1 ,2,3].

title:
  Mass extinctions, biodiversity and mitochondrial function: are bats ‘special’ as reservoirs for emerging viruses?

abstract:
  For the past 10–15 years, bats have attracted growing attention as reservoirs of emerging zoonotic viruses. This has been due to a combination of factors including the emergence of highly virulent zoonotic pathogens, such as Hendra, Nipah, SARS and Ebola viruses, and the high rate of detection of a large number of previously unknown viral sequences in bat specimens. As bats have ancient evolutionary origins and are the only flying mammals, it has been hypothesized that some of their unique biological features may have made them especially suitable hosts for different viruses. So the question ‘Are bats different, special or exceptional?’ has become a focal point in the field of virology, bat biology and virus-host co-evolution. In this brief review, we examine the topic in a relatively unconventional way, that is, our discussion will be based on both scientific discoveries and theoretical predictions. This approach was chosen partially because the data in this field are so limited that it is impossible to conduct a useful review based on published results only and also because we believe it is important to provoke original, speculative or even controversial ideas or theories in this important field of research.


id: cord-276585-m1dkkbq7
title: Viral Host Jumps: Moving toward a Predictive Framework
author: Pulliam, Juliet R. C.
date: 2008-02-13
txt: ./txt/cord-276585-m1dkkbq7.txt
cache: ./cache/cord-276585-m1dkkbq7.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1007/s10393-007-0149-6
doi: 10.1007/s10393-007-0149-6
summary:
  Focusing on the appearance of viral pathogens in new host species, I outline a framework that uses specific molecular characteristics to rank virus families by their expected a priori ability to complete each of three steps in the emergence process (encounter, infection, and propagation). This approach yields predictions consistent with empirical observations regarding the ability of specific viral families to infect novel host species but highlights the need for consideration of other factors, such as the ecology of host interactions and the determinants of cellular susceptibility and permissivity to specific virus groups, when trying to predict the frequency with which a virus will encounter a novel host species or the probability of propagation within a novel host species once infection has occurred. Although he makes no attempt to quantitatively determine the relative frequency of emergence for different types of pathogens, Burke claims that recent pandemics in humans and wildlife have mostly been caused by RNA viruses, citing multiple examples (influenza A, HIV-1, enteroviruses 70 and 71, human T-cell lymphoma virus, three paramyxoviruses, porcine respiratory coronavirus, and a calicivirus that causes hemorrhagic disease in rabbits).

abstract:
  In order to predict pathogen emergence, we must distinguish between emergence phenomena that occur via different processes. Focusing on the appearance of viral pathogens in new host species, I outline a framework that uses specific molecular characteristics to rank virus families by their expected a priori ability to complete each of three steps in the emergence process (encounter, infection, and propagation). I then discuss the degree to which the patterns expected, based solely on molecular-level structural characteristics, agree with observations regarding the ability of animal viruses to infect humans. This approach yields predictions consistent with empirical observations regarding the ability of specific viral families to infect novel host species but highlights the need for consideration of other factors, such as the ecology of host interactions and the determinants of cellular susceptibility and permissivity to specific virus groups, when trying to predict the frequency with which a virus will encounter a novel host species or the probability of propagation within a novel host species once infection has occurred.


id: cord-276637-re9c3e0b
title: Parasites of seabirds: A survey of effects and ecological implications
author: Khan, Junaid S.
date: 2019-04-04
txt: ./txt/cord-276637-re9c3e0b.txt
cache: ./cache/cord-276637-re9c3e0b.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S006528811930001X
doi: 10.1016/bs.amb.2019.02.001
summary:
  In particular, a range of microand macro-parasites can affect seabird species, including ticks, mites, helminths, viruses and bacteria in gulls, terns, skimmers, skuas, auks and selected phalaropes (Charadriiformes), tropicbirds (Phaethontiformes), penguins (Sphenisciformes), tubenoses (Procellariiformes), cormorants, frigatebirds, boobies, gannets (Suliformes), and pelicans (Pelecaniformes) and marine seaducks and loons (Anseriformes and Gaviiformes). Except under extreme conditions where the presence of a parasite has a devastating impact causing widespread mortality (e.g. avian cholera; Butler et al., 2011; Descamps et al., 2012; Friend and Franson, 1999) , little is known about how interactions with these organisms alter seabird health, reproductive success, and ultimately, seabird population viability and evolution. Among arthropods, ticks transmit the greatest variety of infectious agents, including viruses, bacteria, protozoa and even helminths, but most research to date on seabirds has focused on Ixodes spp., which act as vectors of Lyme disease bacteria (Borrelia burgdorferi s.l.; Dantas-Torres et al., 2012; Jongejan and Uilenberg, 2004; Table 1 ).

abstract:
  Parasites are ubiquitous in the environment, and can cause negative effects in their host species. Importantly, seabirds can be long-lived and cross multiple continents within a single annual cycle, thus their exposure to parasites may be greater than other taxa. With changing climatic conditions expected to influence parasite distribution and abundance, understanding current level of infection, transmission pathways and population-level impacts are integral aspects for predicting ecosystem changes, and how climate change will affect seabird species. In particular, a range of micro- and macro-parasites can affect seabird species, including ticks, mites, helminths, viruses and bacteria in gulls, terns, skimmers, skuas, auks and selected phalaropes (Charadriiformes), tropicbirds (Phaethontiformes), penguins (Sphenisciformes), tubenoses (Procellariiformes), cormorants, frigatebirds, boobies, gannets (Suliformes), and pelicans (Pelecaniformes) and marine seaducks and loons (Anseriformes and Gaviiformes). We found that the seabird orders of Charadriiformes and Procellariiformes were most represented in the parasite-seabird literature. While negative effects were reported in seabirds associated with all the parasite groups, most effects have been studied in adults with less information known about how parasites may affect chicks and fledglings. We found studies most often reported on negative effects in seabird hosts during the breeding season, although this is also the time when most seabird research occurs. Many studies report that external factors such as condition of the host, pollution, and environmental conditions can influence the effects of parasites, thus cumulative effects likely play a large role in how parasites influence seabirds at both the individual and population level. With an increased understanding of parasite-host dynamics it is clear that major environmental changes, often those associated with human activities, can directly or indirectly affect the distribution, abundance, or virulence of parasites and pathogens.


id: cord-277417-f71jwdzj
title: The phylogenomics of evolving virus virulence
author: Geoghegan, Jemma L.
date: 2018-10-10
url: https://doi.org/10.1038/s41576-018-0055-5
doi: 10.1038/s41576-018-0055-5
abstract:
  How virulence evolves after a virus jumps to a new host species is central to disease emergence. Our current understanding of virulence evolution is based on insights drawn from two perspectives that have developed largely independently: long-standing evolutionary theory based on limited real data examples that often lack a genomic basis, and experimental studies of virulence-determining mutations using cell culture or animal models. A more comprehensive understanding of virulence mutations and their evolution can be achieved by bridging the gap between these two research pathways through the phylogenomic analysis of virus genome sequence data as a guide to experimental study.


id: cord-288231-vg8bwed9
title: The Application of Genomics to Emerging Zoonotic Viral Diseases
author: Haagmans, Bart L.
date: 2009-10-26
txt: ./txt/cord-288231-vg8bwed9.txt
cache: ./cache/cord-288231-vg8bwed9.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/19855817/
doi: 10.1371/journal.ppat.1000557
summary:
  Other viruses, such as influenza A viruses and severe acute respiratory syndrome coronavirus (SARS-CoV), may need multiple genetic changes to adapt successfully to humans as a new host species; these changes might include differential receptor usage, enhanced replication, evasion of innate and adaptive host immune defenses, and/or increased efficiency of transmission. New molecular techniques such as high-throughput sequencing, mRNA expression profiling, and array-based single nucleotide polymorphism (SNP) analysis provide ways to rapidly identify emerging pathogens (Nipah virus and SARS-CoV, for example) and to analyze the diversity of their genomes as well as the host responses against them. After introduction of a new influenza A virus from an avian or porcine reservoir into the human species, viral genomics studies are essential to identify critical mutations that enable the circulating virus to spread efficiently, interact with different receptors, and cause disease in the new host.

abstract:
  Interspecies transmission of pathogens may result in the emergence of new infectious diseases in humans as well as in domestic and wild animals. Genomics tools such as high-throughput sequencing, mRNA expression profiling, and microarray-based analysis of single nucleotide polymorphisms are providing unprecedented ways to analyze the diversity of the genomes of emerging pathogens as well as the molecular basis of the host response to them. By comparing and contrasting the outcomes of an emerging infection with those of closely related pathogens in different but related host species, we can further delineate the various host pathways determining the outcome of zoonotic transmission and adaptation to the newly invaded species. The ultimate challenge is to link pathogen and host genomics data with biological outcomes of zoonotic transmission and to translate the integrated data into novel intervention strategies that eventually will allow the effective control of newly emerging infectious diseases.


id: cord-289443-46w52de3
title: Evolutionary insights into host–pathogen interactions from mammalian sequence data
author: Sironi, Manuela
date: 2015-03-18
txt: ./txt/cord-289443-46w52de3.txt
cache: ./cache/cord-289443-46w52de3.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1038/nrg3905
doi: 10.1038/nrg3905
summary:
  Nevertheless, natural selection signatures have been described at several mammalian genes that interact with recently emerged human infectious agents (for example, HIV-1), possibly as a result of the pressure imposed by extinct pathogens or because these agents have established long-lasting interactions with non-human hosts. Thus, as observed for ACE2, MERS-CoV and related viruses (for example, coronavirus HKU4) are likely to act as drivers of molecular evolution on mammalian DPP4 genes; it will be especially interesting to evaluate the contribution of positively selected sites in ferrets because these animals are resistant to MERS-CoV infection. In the host-pathogen arms race, these molecules represent one of the foremost detection-defence systems; consistently, several studies have reported adaptive evolution at genes encoding mammalian PRRs. Analyses in primates, rodents and representative mammalian species indicate that positive selection shaped nucleotide diversity at most TLRs, with the strongest pressure acting on TLR4 (REFS 35, 48, 49) .

abstract:
  Infections are one of the major selective pressures acting on humans, and host-pathogen interactions contribute to shaping the genetic diversity of both organisms. Evolutionary genomic studies take advantage of experiments that natural selection has been performing over millennia. In particular, inter-species comparative genomic analyses can highlight the genetic determinants of infection susceptibility or severity. Recent examples show how evolution-guided approaches can provide new insights into host–pathogen interactions, ultimately clarifying the basis of host range and explaining the emergence of different diseases. We describe the latest developments in comparative immunology and evolutionary genetics, showing their relevance for understanding the molecular determinants of infection susceptibility in mammals. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nrg3905) contains supplementary material, which is available to authorized users.


id: cord-290253-hxxizipk
title: Changes in temperature alter the potential outcomes of virus host shifts
author: Roberts, Katherine E.
date: 2018-10-19
txt: ./txt/cord-290253-hxxizipk.txt
cache: ./cache/cord-290253-hxxizipk.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1371/journal.ppat.1007185
doi: 10.1371/journal.ppat.1007185
summary:
  Susceptibility to infection is known to vary with temperature, due to within individual physiological changes in factors such as the host immune response, metabolic rate or behavioural adaptations [22] [23] [24] [25] . However, if the host phylogeny also explains much of the variation in thermal tolerance, then phylogenetic patterns in virus susceptibility could be due to differences between species'' natural thermal optima and the chosen assay temperatures. We infected 45 species of Drosophilidae with Drosophila C Virus (DCV; Dicistroviridae) at three different temperatures and measured how viral load changes with temperature. We also examine how proxies for thermal optima and cellular function (thermal tolerances and basal metabolic rate) relate to virus susceptibility across temperatures, as increasing temperatures may have broad effects on both host and parasite [43] [44] [45] . To investigate the effect of temperature on virus host shifts we quantified viral load in 12,827 flies over 396 biological replicates, from 45 species of Drosophilidae at three temperatures ( Fig 1) .

abstract:
  Host shifts–where a pathogen jumps between different host species–are an important source of emerging infectious disease. With on-going climate change there is an increasing need to understand the effect changes in temperature may have on emerging infectious disease. We investigated whether species’ susceptibilities change with temperature and ask if susceptibility is greatest at different temperatures in different species. We infected 45 species of Drosophilidae with an RNA virus and measured how viral load changes with temperature. We found the host phylogeny explained a large proportion of the variation in viral load at each temperature, with strong phylogenetic correlations between viral loads across temperature. The variance in viral load increased with temperature, while the mean viral load did not. This suggests that as temperature increases the most susceptible species become more susceptible, and the least susceptible less so. We found no significant relationship between a species’ susceptibility across temperatures, and proxies for thermal optima (critical thermal maximum and minimum or basal metabolic rate). These results suggest that whilst the rank order of species susceptibilities may remain the same with changes in temperature, some species may become more susceptible to a novel pathogen, and others less so.


id: cord-290548-0wezrr1b
title: Villains or heroes? The raison d''être of viruses
author: Watanabe, Tokiko
date: 2020-02-19
txt: ./txt/cord-290548-0wezrr1b.txt
cache: ./cache/cord-290548-0wezrr1b.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1002/cti2.1114
doi: 10.1002/cti2.1114
summary:
  For example, Ebola virus disease and acquired immunodeficiency syndrome emerged in 1976 and 1981, respectively, 5-9 and more recently, severe acute respiratory syndrome (SARS), highly pathogenic avian influenza viruses and Middle East respiratory syndrome (MERS) have appeared in human society. In traditional virology, most viruses found in humans are considered to be pathogenic to their hosts; however, recent studies have shown that there are some viruses that have symbiotic relationships with their hosts and do not cause disease. 44 In the last a few decades, emerging infectious diseases caused by newly identified viruses, such as Ebola virus, 5-8 SARS and MERS coronaviruses, [10] [11] [12] human immunodeficiency virus (HIV), 9 Nipah virus and Hendra virus, [45] [46] [47] [48] have appeared in human society. To date, the PREDICT programme has found over 1100 viruses in animals and humans, including a new Ebola virus and MERSand SARS-like coronaviruses.

abstract:
  The relationship between humans and viruses has a long history. Since the first identification of viruses in the 19th century, we have considered them to be ‘pathogens’ and have studied their mechanisms of replication and pathogenicity to combat the diseases that they cause. However, the relationships between hosts and viruses are various and virus infections do not necessarily cause diseases in their hosts. Rather, recent studies have shown that viral infections sometimes have beneficial effects on the biological functions and/or evolution of hosts. Here, we provide some insight into the positive side of viruses.


id: cord-291946-kq0rsuxj
title: The Mongoose, the Pheasant, the Pox, and the Retrovirus
author: Etienne, Lucie
date: 2013-08-27
txt: ./txt/cord-291946-kq0rsuxj.txt
cache: ./cache/cord-291946-kq0rsuxj.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/24013523/
doi: 10.1371/journal.pbio.1001641
summary:
  The genomes of two species of mongooses and an egg-laying mammal called an echidna show that a virus currently present in poultry, the reticuloendotheliosis virus (REV), is actually of ancient exotic mammalian origin. The genomes of two species of mongooses and an egg-laying mammal called an echidna show that a virus currently present in poultry, the reticuloendotheliosis virus (REV), is actually of ancient exotic mammalian origin. Although REV may still exist somewhere in a mammalian host, its modern form links an 8 million-year-old infection of the ancestor of a mongoose to a virus that now is circulating in wild birds through malaria studies in the mid-20 th century. Although REV may still exist somewhere in a mammalian host, its modern form links an 8 million-year-old infection of the ancestor of a mongoose to a virus that now is circulating in wild birds through malaria studies in the mid-20 th century.

abstract:
  Paleovirology is the study of ancient viruses. The existence of a paleovirus can sometimes be detected by virtue of its accidental insertion into the germline of different animal species, which allows one to date when the virus actually existed. However, the ancient and the modern often connect, as modern viruses have unexpected origins that can be traced to ancient infections. The genomes of two species of mongooses and an egg-laying mammal called an echidna show that a virus currently present in poultry, the reticuloendotheliosis virus (REV), is actually of ancient exotic mammalian origin. REV apparently spread to poultry through a circuitous route involving the isolation of malaria parasites from a pheasant from Borneo housed at the Bronx Zoo that was contaminated with REV. Repeated passage of this virus in poultry adapted the virus to its new host. At some point, the virus got inserted into another virus, called fowlpox virus, which has spread back into the wild. Although REV may still exist somewhere in a mammalian host, its modern form links an 8 million-year-old infection of the ancestor of a mongoose to a virus that now is circulating in wild birds through malaria studies in the mid-20(th) century. These lessons of ancient and modern viruses have implications for modern human pandemics from viral reservoirs and for human interventions that may come with unintended consequences.


id: cord-292657-gq3965se
title: Decoding the global outbreak of COVID-19: the nature is behind the scene
author: Das, Piyanki
date: 2020-06-22
txt: ./txt/cord-292657-gq3965se.txt
cache: ./cache/cord-292657-gq3965se.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32656307/
doi: 10.1007/s13337-020-00605-y
summary:
  The rapid evolving nature by changing host body environment and extreme environmental stability, collectively makes SARS-CoV-2 into an extremely virulent genetic variant. Thus both the host body or internal environment and the external environment performs equally as a source, responsible for shaping the genetic evolution of the SARS-CoV-2 towards theCOVID-19 disease fitness in nature in a pandemic form. The probable line of development for such pandemic outcomes happened by continuous evolutionary procedure within different species or host environment exposure, by mutation during replication or genetic recombination between two different viral species and ultimate adaptation to a susceptible host by natural selection of the new version of the viable pathogen resulting infection [7, 8] . Then genetically close different subtypes of SARS-CoV-2 develops unique spike protein receptor binding domain with high degree of receptor binding property to human cells and adapt itself to fit the character inside the host body.

abstract:
  The sudden emergence of SARS-CoV-2 causing the global pandemic is a major public health concern. Though the virus is considered as a novel entity, it is not a completely new member. It is just a new version of previously emerged human SARS corona virus. The rapid evolving nature by changing host body environment and extreme environmental stability, collectively makes SARS-CoV-2 into an extremely virulent genetic variant. The evolution of the virus has been occurred by the continuous process of molecular genetic manipulation, through mutation, deletion and genetic recombinationevents. Different host body environment acts as the supportive system for the pathogen which creates extreme selective pressure. By the process of genetic evolution the pathogen developes new characters. Then the new version of the virus has been naturally selected by susceptible human host and adapt itself inside the host body causing deadly effect. Moreover, extreme environmental stability helps in the process of viral survival outside the host and its transmission. Thus both the host body or internal environment and the external environment performs equally as a source, responsible for shaping the genetic evolution of the SARS-CoV-2 towards theCOVID-19 disease fitness in nature in a pandemic form.


id: cord-296179-hobh6akq
title: Does genetic diversity limit disease spread in natural host populations?
author: King, K C
date: 2012-06-20
txt: ./txt/cord-296179-hobh6akq.txt
cache: ./cache/cord-296179-hobh6akq.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1038/hdy.2012.33
doi: 10.1038/hdy.2012.33
summary:
  (2004) confirmed that the increase in disease susceptibility resulted from a lower frequency of resistance alleles in the population, and not by generalized inbreeding effects. Two models suggest that genetic variation in host susceptibility would not affect infectious disease spread (Springbett et al., 2003; Yates et al., 2006) , but it might reduce the severity of infection (Springbett et al., 2003) . In contrast, Lively (2010a) found that host genetic diversity could reduce the risk of disease spread, assuming that each host genotype was susceptible to a different parasite genotype. The more recent model suggests that increases in the genetic diversity of host populations could have a large effect on disease spread and prevalence at equilibrium (Lively, 2010a) . The available data and the model are consistent with the idea that genetic diversity in host populations can reduce the spread of disease.

abstract:
  It is a commonly held view that genetically homogenous host populations are more vulnerable to infection than genetically diverse populations. The underlying idea, known as the ‘monoculture effect,' is well documented in agricultural studies. Low genetic diversity in the wild can result from bottlenecks (that is, founder effects), biparental inbreeding or self-fertilization, any of which might increase the risk of epidemics. Host genetic diversity could buffer populations against epidemics in nature, but it is not clear how much diversity is required to prevent disease spread. Recent theoretical and empirical studies, particularly in Daphnia populations, have helped to establish that genetic diversity can reduce parasite transmission. Here, we review the present theoretical work and empirical evidence, and we suggest a new focus on finding ‘diversity thresholds.'


id: cord-297960-4x1j0iqg
title: Common Nodes of Virus–Host Interaction Revealed Through an Integrated Network Analysis
author: Bösl, Korbinian
date: 2019-10-04
txt: ./txt/cord-297960-4x1j0iqg.txt
cache: ./cache/cord-297960-4x1j0iqg.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3389/fimmu.2019.02186
doi: 10.3389/fimmu.2019.02186
summary:
  Furthermore, we performed an interactome-informed drug re-purposing screen and identified novel activities for broad-spectrum antiviral agents against hepatitis C virus and human metapneumovirus. Furthermore, we performed an interactome-informed drug re-purposing screen and identified novel activities for broad-spectrum antiviral agents against hepatitis C virus and human metapneumovirus. Global systems-level approaches including functional RNAi screens, interactome mapping technologies such as affinity-purification mass spectrometry (AP-MS), quantitative proteomics, and CRISPR/Cas9-based screens have provided unparalleled details and insights into the dynamics of host proteome in immune cells (21) (22) (23) (24) , host-virus interactome (15-17, 25, 26) , and also identified important host dependency factors of various viruses (25, 27, 28) . We hypothesized that combining a meta-analysis of host-virus protein-protein interactions of multiple viruses and functional RNAi screens would provide novel insights for developing broadspectrum antiviral strategies. High-Definition analysis of host protein stability during human cytomegalovirus infection reveals antiviral factors and viral evasion mechanisms

abstract:
  Viruses are one of the major causes of acute and chronic infectious diseases and thus a major contributor to the global burden of disease. Several studies have shown how viruses have evolved to hijack basic cellular pathways and evade innate immune response by modulating key host factors and signaling pathways. A collective view of these multiple studies could advance our understanding of virus-host interactions and provide new therapeutic perspectives for the treatment of viral diseases. Here, we performed an integrative meta-analysis to elucidate the 17 different host-virus interactomes. Network and bioinformatics analyses showed how viruses with small genomes efficiently achieve the maximal effect by targeting multifunctional and highly connected host proteins with a high occurrence of disordered regions. We also identified the core cellular process subnetworks that are targeted by all the viruses. Integration with functional RNA interference (RNAi) datasets showed that a large proportion of the targets are required for viral replication. Furthermore, we performed an interactome-informed drug re-purposing screen and identified novel activities for broad-spectrum antiviral agents against hepatitis C virus and human metapneumovirus. Altogether, these orthogonal datasets could serve as a platform for hypothesis generation and follow-up studies to broaden our understanding of the viral evasion landscape.


id: cord-298475-3bhiattk
title: Impacts of Covid-19 on peer-to-peer accommodation platforms: Host perceptions and responses
author: Farmaki, Anna
date: 2020-09-03
txt: ./txt/cord-298475-3bhiattk.txt
cache: ./cache/cord-298475-3bhiattk.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.ijhm.2020.102663
doi: 10.1016/j.ijhm.2020.102663
summary:
  The peer-to-peer (P2P) accommodation sector has attempted to follow suit, with platforms such as Airbnb and Booking.com responding to the effects of Covid-19 in numerous ways. In recent years changes have been observed in the P2P accommodation sector as the growth of certain platforms (i.e. Airbnb) and the competition among hosts has led to the adoption of professional hospitality standards (Farmaki and Kaniadakis, 2020; . Within this type of hosts, we also identified participants that were previously involved in long-term renting; yet, they decided to switch to short-term rentals via P2P accommodation platforms as their popularity grew, allowing them to earn more money. Overall, five types of hosts were identified and categorised on a continuum (figure 1) according to their long-term perspective (i.e. decision to continue hosting on P2P accommodation platforms) and level of practice adjustment.

abstract:
  The Covid-19 pandemic has brought international tourism at a standstill. Peer-to-peer (P2P) accommodation, in particular, has been greatly affected with platforms being heavily criticised for lacking a strategic response to users’ needs. Drawing from semi-structured interviews with P2P accommodation hosts, this study aims to explore: a) their perceptions of the short-term impacts of the pandemic on their hosting practice, b) their responses to the pandemic and c) their perceptions of the long-term impacts of the pandemic on the P2P accommodation sector. The study offers a continuum of host pandemic responses which illustrates different types of hosts in relation to their market perspective and intention to continue hosting on P2P platforms. The continuum carries theoretical implications as it offers insights to academics exploring crisis impacts on P2P accommodation. It is also of practical value to platforms and practitioners as it may lead to improved crisis management strategies.


id: cord-299828-fb84rtmx
title: Taming wildlife disease: bridging the gap between science and management
author: Joseph, Maxwell B.
date: 2013-04-16
txt: ./txt/cord-299828-fb84rtmx.txt
cache: ./cache/cord-299828-fb84rtmx.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1111/1365-2664.12084
doi: 10.1111/1365-2664.12084
summary:
  Despite the wealth of empirical WDM research, management outcomes can be difficult to predict because system-specific information is lacking for novel pathogens and many theoretical concepts in disease ecology (see Table 1 for a subset) have not been widely tested in the field, leading to uncertainty in their generality. Corridor vaccination can reduce disease in metapopulations; movement controls are unlikely to work for chronic infections Keeling & Eames (2005) Transmission increases with host density Host density reductions may reduce disease transmission, and density thresholds for disease persistence may exist Anderson & May (1979) Transmission increases with disease prevalence independent of host density Transmission associated with sexual interactions is more likely to cause host extinction, and non-selective culling may not reduce transmission Getz & Pickering (1983) Predation as a regulator of host population and disease We use a quantitative, case-based approach to provide a critical retrospective of WDM over the last four decades to: (i) quantify how frequently specific theoretical concepts from disease ecology have been applied in the literature, (ii) identify prevailing management objectives, groups and reported outcomes and (iii) assess taxonomic biases in WDM literature.

abstract:
  1. Parasites and pathogens of wildlife can threaten biodiversity, infect humans and domestic animals, and cause significant economic losses, providing incentives to manage wildlife diseases. Recent insights from disease ecology have helped transform our understanding of infectious disease dynamics and yielded new strategies to better manage wildlife diseases. Simultaneously, wildlife disease management (WDM) presents opportunities for large‐scale empirical tests of disease ecology theory in diverse natural systems. 2. To assess whether the potential complementarity between WDM and disease ecology theory has been realized, we evaluate the extent to which specific concepts in disease ecology theory have been explicitly applied in peer‐reviewed WDM literature. 3. While only half of WDM articles published in the past decade incorporated disease ecology theory, theory has been incorporated with increasing frequency over the past 40 years. Contrary to expectations, articles authored by academics were no more likely to apply disease ecology theory, but articles that explain unsuccessful management often do so in terms of theory. 4. Some theoretical concepts such as density‐dependent transmission have been commonly applied, whereas emerging concepts such as pathogen evolutionary responses to management, biodiversity–disease relationships and within‐host parasite interactions have not yet been fully integrated as management considerations. 5. Synthesis and applications. Theory‐based disease management can meet the needs of both academics and managers by testing disease ecology theory and improving disease interventions. Theoretical concepts that have received limited attention to date in wildlife disease management could provide a basis for improving management and advancing disease ecology in the future.


id: cord-305327-hayhbs5u
title: Global Spread of Hemorrhagic Fever Viruses: Predicting Pandemics
author: Gonzalez, Jean-Paul
date: 2017-09-19
txt: ./txt/cord-305327-hayhbs5u.txt
cache: ./cache/cord-305327-hayhbs5u.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1007/978-1-4939-6981-4_1
doi: 10.1007/978-1-4939-6981-4_1
summary:
  Other pathogens that are remarkable for their epidemic expansions include the arenavirus hemorrhagic fevers and hantavirus diseases carried by rodents over great geographic distances and the arthropod-borne viruses (West Nile, chikungunya and Zika) enabled by ecology and vector adaptations. Emergence from a sporadic case to an outbreak, to an epidemic, and ultimately to a pandemic depends upon effective transmission among nonimmune hosts, host availability (density), characteristics of the vector (natural or human made) that would enable it to circumvent distances, and the pathogen infectiousness. Although MARV expansion appears to be limited to a few countries in Africa, the recent emergence (estimated at a few decades ago) of a second human pathogenic marburgvirus known as Ravn virus, and the widely distributed Old World rousette fruit bats (Rousettus spp.) serving as reservoir for both viruses [45] , are two factors that favor pandemic risk.

abstract:
  As successive epidemics have swept the world, the scientific community has quickly learned from them about the emergence and transmission of communicable diseases. Epidemics usually occur when health systems are unprepared. During an unexpected epidemic, health authorities engage in damage control, fear drives action, and the desire to understand the threat is greatest. As humanity recovers, policy-makers seek scientific expertise to improve their “preparedness” to face future events. Global spread of disease is exemplified by the spread of yellow fever from Africa to the Americas, by the spread of dengue fever through transcontinental migration of mosquitos, by the relentless influenza virus pandemics, and, most recently, by the unexpected emergence of Ebola virus, spread by motorbike and long haul carriers. Other pathogens that are remarkable for their epidemic expansions include the arenavirus hemorrhagic fevers and hantavirus diseases carried by rodents over great geographic distances and the arthropod-borne viruses (West Nile, chikungunya and Zika) enabled by ecology and vector adaptations. Did we learn from the past epidemics? Are we prepared for the worst? The ultimate goal is to develop a resilient global health infrastructure. Besides acquiring treatments, vaccines, and other preventive medicine, bio-surveillance is critical to preventing disease emergence and to counteracting its spread. So far, only the western hemisphere has a large and established monitoring system; however, diseases continue to emerge sporadically, in particular in Southeast Asia and South America, illuminating the imperfections of our surveillance. Epidemics destabilize fragile governments, ravage the most vulnerable populations, and threaten the global community. Pandemic risk calculations employ new technologies like computerized maintenance of geographical and historical datasets, Geographic Information Systems (GIS), Next Generation sequencing, and Metagenomics to trace the molecular changes in pathogens during their emergence, and mathematical models to assess risk. Predictions help to pinpoint the hot spots of emergence, the populations at risk, and the pathogens under genetic evolution. Preparedness anticipates the risks, the needs of the population, the capacities of infrastructure, the sources of emergency funding, and finally, the international partnerships needed to manage a disaster before it occurs. At present, the world is in an intermediate phase of trying to reduce health disparities despite exponential population growth, political conflicts, migration, global trade, urbanization, and major environmental changes due to global warming. For the sake of humanity, we must focus on developing the necessary capacities for health surveillance, epidemic preparedness, and pandemic response.


id: cord-307803-rlvk6bcx
title: Q&A: What are pathogens, and what have they done to and for us?
author: Balloux, Francois
date: 2017-10-19
txt: ./txt/cord-307803-rlvk6bcx.txt
cache: ./cache/cord-307803-rlvk6bcx.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1186/s12915-017-0433-z
doi: 10.1186/s12915-017-0433-z
summary:
  Infectious diseases have historically represented the most common cause of death in humans until recently, exceeding by far the toll taken by wars or famines. Conversely, Yersinia pestis, another intracellular obligate bacterium and the agent of plague, has a natural life cycle involving alternating infections of rodents and fleas, but can infect essentially any mammalian host. Apart from a few putative ancestral pathogens, including Helicobacter pylori [15] , that might have co-speciated with their human host, the infectious diseases afflicting us were acquired through host jumps from other wild or domesticated animal hosts or sometimes from the wider environment. We might also speculate that the evolutionary potential and high genetic diversity of most pathogens limits our ability to detect protective variants in the human genome, particularly so if these were only effective against a subset of lineages within a pathogenic species.

abstract:
  Microbes are found on us, within us and around us. They inhabit virtually every environment on the planet and the bacteria carried by an average human, mostly in their gut, outnumber human cells. The vast majority of microbes are harmless to us, and many play essential roles in plant, animal and human health. Others, however, are either obligate or facultative pathogens exerting a spectrum of deleterious effects on their hosts. Infectious diseases have historically represented the most common cause of death in humans until recently, exceeding by far the toll taken by wars or famines. From the dawn of humanity and throughout history, infectious diseases have shaped human evolution, demography, migrations and history.


id: cord-309642-wwaa6ls0
title: Pathogenesis of Viral Infections
author: Potgieter, Leon N.D.
date: 1986-11-30
url: https://api.elsevier.com/content/article/pii/S0195561686501297
doi: 10.1016/s0195-5616(86)50129-7
abstract:
  The article considers factors that influence pathogenesis, initiation of infection, dissemination of virus within a host, lytic viral infections, viral immunosuppression, viral immunopathology, and viral oncogenesis.


id: cord-312545-io2jmp7o
title: Ecosystem dynamics, biological diversity and emerging infectious diseases
author: Roche, Benjamin
date: 2011-04-30
txt: ./txt/cord-312545-io2jmp7o.txt
cache: ./cache/cord-312545-io2jmp7o.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S1631069111000709
doi: 10.1016/j.crvi.2011.02.008
summary:
  Finally, we propose some research avenues that take better into account the multi-host species reality in the transmission of the most important emerging infectious diseases, and, particularly, suggest, as a possible orientation, the careful assessment of the life-history characteristics of hosts and vectors in a community ecology-based perspective. Finally, we propose some research avenues that take better into account the multi-host species reality in the transmission of the most important emerging infectious diseases, and, particularly, suggest, as a possible orientation, the careful assessment of the life-history characteristics of hosts and vectors in a community ecology-based perspective. This raises two important questions concerning: (i) the effects on local disease transmission of the accidental introduction or biological invasion by exotic vectors, even when they show a low competence to transmit the infection; and (ii) the role of low to very low In species-rich reservoir communities, generally a decrease in the prevalence of disease pathogens in the vectors is observed.

abstract:
  In this article, we summarize the major scientific developments of the last decade on the transmission of infectious agents in multi-host systems. Almost sixty percent of the pathogens that have emerged in humans during the last 30–40 years are of animal origin and about sixty percent of them show an important variety of host species besides humans (3 or more possible host species). In this review, we focus on zoonotic infections with vector-borne transmission and dissect the contrasting effects that a multiplicity of host reservoirs and vectors can have on their disease dynamics. We discuss the effects exerted by host and vector species richness and composition on pathogen prevalence (i.e., reduction, including the dilution effect, or amplification). We emphasize that, in multiple host systems and for vector-borne zoonotic pathogens, host reservoir species and vector species can exert contrasting effect locally. The outcome on disease dynamics (reduced pathogen prevalence in vectors when the host reservoir species is rich and increased pathogen prevalence when the vector species richness increases) may be highly heterogeneous in both space and time. We then ask briefly how a shift towards a more systemic perspective in the study of emerging infectious diseases, which are driven by a multiplicity of hosts, may stimulate further research developments. Finally, we propose some research avenues that take better into account the multi-host species reality in the transmission of the most important emerging infectious diseases, and, particularly, suggest, as a possible orientation, the careful assessment of the life-history characteristics of hosts and vectors in a community ecology-based perspective.


id: cord-313301-7mkadtp9
title: EVOLUTION OF HOST SPECIFICITY DRIVES REPRODUCTIVE ISOLATION AMONG RNA VIRUSES
author: Duffy, Siobain
date: 2007-08-23
txt: ./txt/cord-313301-7mkadtp9.txt
cache: ./cache/cord-313301-7mkadtp9.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/17908251/
doi: 10.1111/j.1558-5646.2007.00226.x
summary:
  In particular, the high pernucleotide mutation rates of RNA viruses (Drake 1993) provide extensive genetic variation that fuels evolution by natural selection, making the study of reproductive isolation and speciation especially feasible (Holmes 2004) . We tested the plausibility of the no-gene mechanism of speciation by examining the consequences of adaptation to a novel host in laboratory populations of the RNA phage 6, which infects a number of Pseudomonas species. The same microevolutionary processes of mutation and natural selection, which led to the adaptation of 6 populations to a novel host also resulted in a macroevolutionary event: the evolution of a new virus species that is reproductively isolated from the ancestral phage 6 wt . Beyond uniquely demonstrating the evolution of reproductive isolation in the laboratory, our study extends the literature describing the evolutionary genetics of narrowed host range when viruses adapt to a single host.

abstract:
  Ecological speciation hypotheses claim that assortative mating evolves as a consequence of divergent natural selection for ecologically important traits. Reproductive isolation is expected to be particularly likely to evolve by this mechanism in species such as phytophagous insects that mate in the habitats in which they eat. We tested this expectation by monitoring the evolution of reproductive isolation in laboratory populations of an RNA virus that undergoes genetic exchange only when multiple virus genotypes coinfect the same host. We subjected four populations of the RNA bacteriophage φ6 to 150 generations of natural selection on a novel host. Although there was no direct selection acting on host range in our experiment, three of the four populations lost the ability to infect one or more alternative hosts. In the most extreme case, one of the populations evolved a host range that does not contain any of the hosts infectible by the wild‐type φ6. Whole genome sequencing confirmed that the resulting reproductive isolation was due to a single nucleotide change, highlighting the ease with which an emerging RNA virus can decouple its evolutionary fate from that of its ancestor. Our results uniquely demonstrate the evolution of reproductive isolation in allopatric experimental populations. Furthermore, our data confirm the biological credibility of simple “no‐gene” mechanisms of assortative mating, in which this trait arises as a pleiotropic effect of genes responsible for ecological adaptation.


id: cord-314325-nquov2i0
title: Epidemiology of Human and Animal Viral Diseases
author: Murphy, F.A.
date: 2008-07-30
txt: ./txt/cord-314325-nquov2i0.txt
cache: ./cache/cord-314325-nquov2i0.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/B9780123744104003903
doi: 10.1016/b978-012374410-4.00390-3
summary:
  Viral disease epidemiology has come to have a major role in clarifying the etiologic role of particular viruses and viral variants as the cause of specific diseases, in improving our understanding of the overall nature of specific viral diseases, and in determining factors affecting host susceptibility and immunity, in unraveling modes of transmission, in clarifying the interaction of viruses with environmental determinants of disease, in determining the safety, efficacy, and utility of vaccines and antiviral drugs, and especially in alerting and directing disease prevention and control actions. Epidemiology is also effective in (1) clarifying the role of particular viruses and viral variants as the cause of disease, (2) clarifying the interaction of viruses with environmental determinants of disease, (3) determining factors affecting host susceptibility, (4) unraveling modes of transmission, and (5) field testing of vaccines and antiviral drugs.

abstract:
  Viral disease epidemiology is the study of the determinants, dynamics, and distribution of viral diseases in populations. The risk of infection or disease in a population is determined by characteristics of the virus, the host, and the host population, as well as behavioral, environmental, and ecological factors that affect virus transmission from one host to another. Viral disease epidemiology has come to have a major role in clarifying the etiologic role of particular viruses and viral variants as the cause of specific diseases, in improving our understanding of the overall nature of specific viral diseases, and in determining factors affecting host susceptibility and immunity, in unraveling modes of transmission, in clarifying the interaction of viruses with environmental determinants of disease, in determining the safety, efficacy, and utility of vaccines and antiviral drugs, and especially in alerting and directing disease prevention and control actions. Information on incidence, prevalence, and morbidity and mortality rates contributes directly to the establishment of priorities for prevention and control programs, whether this involves vaccine or drug development and delivery, environmental and hygienic improvements, enhancement of nutritional status, personal or community behavior, agricultural and food processing enhancements, reservoir host and vector control, and international cooperation and communication.


id: cord-319448-gt6uqfrl
title: The damage-response framework of microbial pathogenesis
author: Casadevall, Arturo
date: 2003
txt: ./txt/cord-319448-gt6uqfrl.txt
cache: ./cache/cord-319448-gt6uqfrl.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/15040176/
doi: 10.1038/nrmicro732
summary:
  Host-microorganism interactions that result in the clearance and/or control of a microorganism without the development of clinically relevant host damage represent a basis for the development of vaccines and immune-response-based therapies for infectious diseases. However, host-induced cell and/or tissue damage can also produce detrimental outcomes, which can result in disease or death -although certain manifestations of host damage represent the outcome of a successful immune response to MICROBIAL INFECTION. To address this impediment to studies of host-microorganism interactions, we propose a new theoretical approach to understanding microbial pathogenesis, known as the ''damage-response'' framework. The central tenets of the ''damage-response'' framework -that the outcome of microbial pathogenesis is the result of a host-microorganism interaction, and that the relevant outcome of this interaction is host damage -provide the basis for a new pathogen-classification scheme. The use of host damage to classify the outcome of a host-microorganism interaction acknowledges and accounts for the contribution of the host immune response to microbial pathogenicity and virulence.

abstract:
  The late twentieth century witnessed the emergence of numerous infectious diseases that are caused by microorganisms that rarely cause disease in normal, healthy immunocompetent hosts. The emergence of these diseases shows that the existing concepts of pathogenicity and virulence do not take into account the fact that both the microorganism and the host contribute to microbial pathogenesis. To address this impediment to studies of host–microorganism interactions, we propose a new theoretical approach to understanding microbial pathogenesis, known as the 'damage-response' framework.


id: cord-319658-u0wjgw50
title: Structural host-microbiota interaction networks
author: Guven-Maiorov, Emine
date: 2017-10-12
txt: ./txt/cord-319658-u0wjgw50.txt
cache: ./cache/cord-319658-u0wjgw50.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1371/journal.pcbi.1005579
doi: 10.1371/journal.pcbi.1005579
summary:
  To date, challenges in experimental techniques limit large-scale characterization of HMIs. Here we highlight an area in its infancy which we believe will increasingly engage the computational community: predicting interactions across kingdoms, and mapping these on the host cellular networks to figure out how commensal and pathogenic microbiota modulate the host signaling and broadly cross-species consequences. Systems biology approaches that integrate the HMIs with host endogenous protein interaction networks reveal the systematic trends in virulence strategies of pathogens. The availability of genome-wide high throughput omics data makes it possible to associate microbiota with certain host phenotypes at multiple levels and construct host-pathogen interaction networks at the transcriptome [21], proteome Combinatorial effects of microbial effectors and the active host pathways determine the cell response. Mimicry of interactions of critical regulatory nodes in core network modules in the immune system, may be a major way through which pathogens adversely subvert-and commensal microbiota may beneficially modulate-the host cell.

abstract:
  Hundreds of different species colonize multicellular organisms making them “metaorganisms”. A growing body of data supports the role of microbiota in health and in disease. Grasping the principles of host-microbiota interactions (HMIs) at the molecular level is important since it may provide insights into the mechanisms of infections. The crosstalk between the host and the microbiota may help resolve puzzling questions such as how a microorganism can contribute to both health and disease. Integrated superorganism networks that consider host and microbiota as a whole–may uncover their code, clarifying perhaps the most fundamental question: how they modulate immune surveillance. Within this framework, structural HMI networks can uniquely identify potential microbial effectors that target distinct host nodes or interfere with endogenous host interactions, as well as how mutations on either host or microbial proteins affect the interaction. Furthermore, structural HMIs can help identify master host cell regulator nodes and modules whose tweaking by the microbes promote aberrant activity. Collectively, these data can delineate pathogenic mechanisms and thereby help maximize beneficial therapeutics. To date, challenges in experimental techniques limit large-scale characterization of HMIs. Here we highlight an area in its infancy which we believe will increasingly engage the computational community: predicting interactions across kingdoms, and mapping these on the host cellular networks to figure out how commensal and pathogenic microbiota modulate the host signaling and broadly cross-species consequences.


id: cord-320083-0k15w624
title: Microbial Virulence Factors
author: Leitão, Jorge H.
date: 2020-07-27
txt: ./txt/cord-320083-0k15w624.txt
cache: ./cache/cord-320083-0k15w624.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32727013/
doi: 10.3390/ijms21155320
summary:
  Microbial virulence factors encompass a wide range of molecules produced by pathogenic microorganisms, enhancing their ability to evade their host defenses and cause disease [...]. The paper focused on the discovery, properties and substrate specificity of the two proteases, their high specificity towards actin, and discussed their contribution to the invasiveness of Serratia, although further knowledge of the bacterium virulence factors and the cellular response mechanisms is required to fully understand the mechanism of Serratia invasion of the host cell [14] . The roles played by virulence factors produced by bacteria when crossing the central nervous system is also addressed, followed by the review of the specific traits of bacterial species more commonly associated with meningitis [15] . The authors also present a thorough review of the main virulence factors used by the organism, including pyolysin, fimbriae, extracellular matrix-binding proteins, neuraminidases, and ability to form biofilms [17] . From Gene to Protein-How Bacterial Virulence Factors Manipulate Host Gene Expression during Infection

abstract:
  Microbial virulence factors encompass a wide range of molecules produced by pathogenic microorganisms, enhancing their ability to evade their host defenses and cause disease [...].


id: cord-324697-c0dv1zmi
title: Fated for decay: RNA elements targeted by viral endonucleases
author: Rodriguez, William
date: 2020-06-07
txt: ./txt/cord-324697-c0dv1zmi.txt
cache: ./cache/cord-324697-c0dv1zmi.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.semcdb.2020.05.010
doi: 10.1016/j.semcdb.2020.05.010
summary:
  Consequently, viruses have evolved an arsenal of strategies to target these RNA features and ultimately take control of the pathways they influence, and these strategies contribute to the global shutdown of the host gene expression machinery known as "Host Shutoff". Throughout this section we will discuss how each of these RNA features render mRNA susceptible toand in many cases directviral endonuclease cleavage or similar strategies aimed at degradation of the host transcriptome during viral infection. Nsp1 thus emerges as a thorough RNA decay trigger that uses diverse and non-overlapping strategies to widely target host mRNAs. How the viral transcripts escape nsp-1 mediated is still under investigation. Overall, SARS coronavirus nsp1 is an interesting regulator of RNA stability: currently, nsp1 does not appear to have any endonucleolytic activity of its own, and instead binds to the 40 s subunit exploiting the host''s RNA quality control pathways to trigger mRNA degradation. Vaccinia virus D10 protein has mRNA decapping activity, providing a mechanism for control of host and viral gene expression

abstract:
  For over a decade, studies of messenger RNA regulation have revealed an unprecedented level of connectivity between the RNA pool and global gene expression. These connections are underpinned by a vast array of RNA elements that coordinate RNA-protein and RNA-RNA interactions, each directing mRNA fate from transcription to translation. Consequently, viruses have evolved an arsenal of strategies to target these RNA features and ultimately take control of the pathways they influence, and these strategies contribute to the global shutdown of the host gene expression machinery known as “Host Shutoff”. This takeover of the host cell is mechanistically orchestrated by a number of non-homologous virally encoded endoribonucleases. Recent large-scale screens estimate that over 70 % of the host transcriptome is decimated by the expression of these viral nucleases. While this takeover strategy seems extraordinarily well conserved, each viral endonuclease has evolved to target distinct mRNA elements. Herein, we will explore each of these RNA structures/sequence features that render messenger RNA susceptible or resistant to viral endonuclease cleavage. By further understanding these targeting and escape mechanisms we will continue to unravel untold depths of cellular RNA regulation that further underscores the integral relationship between RNA fate and the fate of the cell.


id: cord-329149-1giy1fow
title: Technologies for Proteome-Wide Discovery of Extracellular Host-Pathogen Interactions
author: Martinez-Martin, Nadia
date: 2017-02-22
txt: ./txt/cord-329149-1giy1fow.txt
cache: ./cache/cord-329149-1giy1fow.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/28321417/
doi: 10.1155/2017/2197615
summary:
  Despite SPR and related methods offering higher sensitivity for detection of transient Biochemical and MS PDGFR identified as a high affinity cell surface receptor for the CMV gHgLgO protein complex [21] Herpes simplex viruses (HSVs) Biophysical Secreted and plasma membrane-expressed glycoprotein G targets a specific set of human chemokines with high affinity [22] Human immunodeficiency virus type 1 (HIV) Despite the undoubted importance of the biochemical and biophysical approaches to the study of host-pathogen interactions, the aforementioned limitations have motivated the development of alternative technologies for large-scale analysis of ePPIs. From the initial utilization of microarrays for detection of PPI over a decade ago, human proteome chips containing thousands of recombinant proteins have been generated, some of which are now commercially available.

abstract:
  Pathogens have evolved unique mechanisms to breach the cell surface barrier and manipulate the host immune response to establish a productive infection. Proteins exposed to the extracellular environment, both cell surface-expressed receptors and secreted proteins, are essential targets for initial invasion and play key roles in pathogen recognition and subsequent immunoregulatory processes. The identification of the host and pathogen extracellular molecules and their interaction networks is fundamental to understanding tissue tropism and pathogenesis and to inform the development of therapeutic strategies. Nevertheless, the characterization of the proteins that function in the host-pathogen interface has been challenging, largely due to the technical challenges associated with detection of extracellular protein interactions. This review discusses available technologies for the high throughput study of extracellular protein interactions between pathogens and their hosts, with a focus on mammalian viruses and bacteria. Emerging work illustrates a rich landscape for extracellular host-pathogen interaction and points towards the evolution of multifunctional pathogen-encoded proteins. Further development and application of technologies for genome-wide identification of extracellular protein interactions will be important in deciphering functional host-pathogen interaction networks, laying the foundation for development of novel therapeutics.


id: cord-330590-nu8ckeud
title: Viral metacommunities associated to bats and rodents at different spatial scales
author: Nieto-Rabiela, F.
date: 2018-12-30
txt: ./txt/cord-330590-nu8ckeud.txt
cache: ./cache/cord-330590-nu8ckeud.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32218712/
doi: 10.1556/168.2018.19.2.9
summary:
  We tested the hypothesis that distributions of virus species and viral families from rodents and bats are defined by shared responses to host phylogeny and host functional characteristics, shaping the viral metacommunity structures at four spatial scales (Continental, Biogeographical, Zoogeographical, and Regional). Metacommunity theory implemented in viral communities at different spatial scales in combination with a redundancy analysis allows identifying the factors that facilitate virus distribution among hosts (Mihaljevic 2012 , Dallas and Presley 2014 , Suzán et al. To measure the influence of the host phylogeny and functional characteristics of the host on viral community structure we hypothesized that both the expression of Clementsian structures based on the Niche Theory would prevail at different macroecological scales, and the host phylogeny will explain the viral metacommunity distribution as response of the shared host evolutionary histories and ecological relationships.

abstract:
  One of the main goals of community ecology is to measure the relative importance of environmental filters to understand patterns of species distribution at different temporal and spatial scales. Likewise, the identification of factors that shape symbiont metacommunity structures is important in disease ecology because resulting structures drive disease transmission. We tested the hypothesis that distributions of virus species and viral families from rodents and bats are defined by shared responses to host phylogeny and host functional characteristics, shaping the viral metacommunity structures at four spatial scales (Continental, Biogeographical, Zoogeographical, and Regional). The contribution of host phylogeny and host traits to the metacommunity of viruses at each spatial scale was calculated using a redundant analysis of canonical ordering (RDA). For rodents, at American Continental scale the coherence of viral species metacommunity increased while the spatial scale decreased and Quasi-Clementsian structures were observed. This pattern suggests a restricted distribution of viruses through their hosts, while in the Big Mass (Europe, Africa, and Asia), the coherence decreased as spatial scale decreased. Viral species metacommunities associated with bats was dominated by random structures along all spatial scales. We suggest that this random pattern is a result of the presence of viruses with high occupancy range such as rabies (73%) and coronavirus (27%), that disrupt such structures. At viral family scale, viral metacommunities associated with bats showed coherent structures, with the emergence of Quasi- Clementsian and Checkerboard structures. RDA analysis indicates that the assemblage of viral diversity associated with rodents and bats responds to phylogenetic and functional characteristics, which alternate between spatial scales. Several of these variations could be subject to the spatial scale, in spite of this, we could identify patterns at macro ecological scale. The application of metacommunity theory at symbiont scales is particularly useful for large-scale ecological analysis. Understanding the rules of host-virus association can be useful to take better decisions in epidemiological surveillance, control and even predictions of viral distribution and dissemination. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available for this article at 10.1556/168.2018.19.2.9 and is accessible for authorized users.


id: cord-335774-15fhg8o9
title: Ecology of Neglected Rodent-Borne American Orthohantaviruses
author: Mull, Nathaniel
date: 2020-04-26
txt: ./txt/cord-335774-15fhg8o9.txt
cache: ./cache/cord-335774-15fhg8o9.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32357540/
doi: 10.3390/pathogens9050325
summary:
  Information regarding the presence and genetic diversity of many orthohantaviruses throughout the distributional range of their hosts is minimal and would significantly benefit from virus isolations to indicate a reservoir role. However, mammals, particularly rodents, are still the most common natural hosts of hantaviruses, encompassing viruses in the largest subfamily (Mammantavirinae) and genus (Orthohantavirus) [9] , and only rodent-borne orthohantaviruses have been linked to human disease [10] . For example, range expansion of a North American grassland rodent species, Baiomys taylori, was recently found in New Mexico, United States, likely due to an increase in grassland areas, particularly along roadsides, due to climate change and habitat disturbance [61] . In the absence of empirical data, we shed light on the diversity, transmission, and risk of spillover for neglected American orthohantaviruses and viral genotypes using the ecology of their hosts and information on ANDV and SNV. Since multiple rodent species are commonly found RT-PCR positive for particular American orthohantavirus strains (Table A1) , virus-host relationships are unclear.

abstract:
  The number of documented American orthohantaviruses has increased significantly over recent decades, but most fundamental research has remained focused on just two of them: Andes virus (ANDV) and Sin Nombre virus (SNV). The majority of American orthohantaviruses are known to cause disease in humans, and most of these pathogenic strains were not described prior to human cases, indicating the importance of understanding all members of the virus clade. In this review, we summarize information on the ecology of under-studied rodent-borne American orthohantaviruses to form general conclusions and highlight important gaps in knowledge. Information regarding the presence and genetic diversity of many orthohantaviruses throughout the distributional range of their hosts is minimal and would significantly benefit from virus isolations to indicate a reservoir role. Additionally, few studies have investigated the mechanisms underlying transmission routes and factors affecting the environmental persistence of orthohantaviruses, limiting our understanding of factors driving prevalence fluctuations. As landscapes continue to change, host ranges and human exposure to orthohantaviruses likely will as well. Research on the ecology of neglected orthohantaviruses is necessary for understanding both current and future threats to human health.


id: cord-337738-2qck1j1w
title: Buying time: Drug repurposing to treat the host in COVID‐19H
author: Martin, Jennifer H.
date: 2020-06-23
txt: ./txt/cord-337738-2qck1j1w.txt
cache: ./cache/cord-337738-2qck1j1w.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32578336/
doi: 10.1002/prp2.620
summary:
  COVID19, drug repurposing, global collaboration, host response, renin-angiotensin 2 of 3 | COMMENTARY a further 1-5 years to complete necessary studies, and finalise the regulatory pharmaceutics dossier, but even then, time is still needed to find funding to manufacture, upscale, and develop supply lines to roll it out globally. An approach based on treating the host built on sound physiology and pathophysiology, together with thorough administrative data input and accepted principles of drug repurposing based upon pharmacology and clinical pharmacology is needed. • An international approach to rapidly identify drugs that treat the host in a pandemic to permit time for vaccine and antiviral development. 12 Such a program can provide adequate time for the development of vaccines, serum-based approaches or antiviral drugs, and separately will provide a therapeutic insurance with the inevitable easing of social isolation. Buying time: Drug repurposing to treat the host in COVID-19H

abstract:
  In 2016 Fedson stated …. “For almost two decades, leading scientists and health officials have warned that we must prepare for a potentially devastating global pandemic of an infectious disease. Initial concern was focused on …H5N1…. More recently…a devastating outbreak of Ebola virus..(and) several other emerging viruses are believed to seriously threaten global health and global security. To prepare, scientists have been urged to discover new vaccines and treatments for these emerging viruses. At the same time, political leaders have been urged by global health experts to invest millions in a “top down” restructuring of the global health system. This article takes a different view. It focuses on an alternative approach to the scientific discovery of treatments for individual patients, reviews the mechanisms of action and clinical experience with specific drugs that might be useful, and considers whether or not recent lessons regarding this “bottom up” approach to treatment have been learned”. Now with a new virus and pandemic upon us, Fedson's 2016 comments appear chilling, are cause for reflection on what we have learnt and importantly offer focus on an immediate opportunity in the area of treating the host (Fedson DS, Ann Transl Med, 2016;4:421).


id: cord-338804-nreqluol
title: Viral Pathogenesis
author: Heise, M.T.
date: 2014-11-28
txt: ./txt/cord-338804-nreqluol.txt
cache: ./cache/cord-338804-nreqluol.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/B9780128012383000799
doi: 10.1016/b978-0-12-801238-3.00079-9
summary:
  Viral interactions with these receptors can have a significant impact upon several aspects of viral pathogenesis, including determining the cell or tissue tropism of a virus or even whether a virus can efficiently infect and cause disease in a specific host species. Therefore, viruses that are defective in their ability to antagonize the host type I interferon system are often unable to replicate and spread efficiently within the host, illustrating the importance of viral immune evasion strategies in determining whether a virus will be pathogenic ( Figure 2) . (b) If the virus effectively interferes with the type I interferon response, interferon will be prevented from inducing a robust antiviral state within the host, and the virus is able to replicate to higher levels, will spread more efficiently, and may cause more severe disease. Therefore, like other aspects of viral pathogenesis, a complex series of virus-host interactions determines whether infection with cancer associated viruses ultimately results in disease development.

abstract:
  Viral pathogenesis describes the processes by which viral infections cause diseases and involves virus–host interactions at the cellular and systemic level that determine whether a virus will cause a disease, what form that disease takes, and how severe the disease will be. Though the pathogenesis of each virus is unique, there are several common points in the virus life cycle that are shared between all pathogenic viruses, and by considering these common aspects of the virus-induced disease process, we can explore some general concepts in viral pathogenesis while illustrating some of the virus specific processes that shape disease outcomes.


id: cord-345157-fhmhpobi
title: Virus infection-induced host mRNA degradation and potential application of live cell imaging
author: Qi, Dan
date: 2018-12-12
txt: ./txt/cord-345157-fhmhpobi.txt
cache: ./cache/cord-345157-fhmhpobi.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.jrid.2018.12.002
doi: 10.1016/j.jrid.2018.12.002
summary:
  Herein, we focus on several possible mechanisms of infection-induced host RNA turnover, which seems to be a common strategy for both prokaryotic and eukaryotic viruses during the very early stage of infection and a potential application of live cell imaging on its visualization. Many viruses also impair the translation of cellular mRNA [1e3], one of the mechanisms during the shift of gene expression from host to virus, a process termed "host shutoff", in order to prevent the production of anti-viral, host protecting proteins [4] . Moreover, Gaglia et al.''s work showed that viral encoded proteins trigger host mRNA degradation by a primary endonucleolytic cleavage causing shutoff of host gene expression and a host exonuclease such as Xrn1, an important 5 0 to 3 0 exonuclease in human cells, were required in subsequent completion of host mRNA turnover [5] .

abstract:
  Viruses exist wherever there is life. They can cause allergy, immune response, inflammation, and even fatal diseases directly or indirectly. Accumulating evidence shows that host RNA undergoes rapid degradation during virus infection. Herein, we focus on several possible mechanisms of infection-induced host RNA turnover, which seems to be a common strategy for both prokaryotic and eukaryotic viruses during the very early stage of infection and a potential application of live cell imaging on its visualization.


id: cord-345654-vyz6f3he
title: Evolutionary ecology of virus emergence
author: Dennehy, John J.
date: 2016-12-30
txt: ./txt/cord-345654-vyz6f3he.txt
cache: ./cache/cord-345654-vyz6f3he.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/28036113/
doi: 10.1111/nyas.13304
summary:
  Virus emergence requires overlap between host populations, alterations in virus genetics to permit infection of new hosts, and adaptation to novel hosts such that between‐host transmission is sustainable, all of which are the purview of the fields of ecology and evolution. I argue that, while virus acquisition of the ability to infect new hosts is not difficult, limited evolutionary trajectories to sustained virus between‐host transmission and the combined effects of mutational meltdown, bottlenecking, demographic stochasticity, density dependence, and genetic erosion in ecological sinks limit most emergence events to dead‐end spillover infections. Virus quasispecies may facilitate host range expansion Viruses are among the smallest nucleic acid-based replicating entities and possess characteristics associated with exceptionally fast evolutionary change: small genomes, short generation times, high mutation rates, large population sizes, high levels of genetic diversity, and strong selection pressures.

abstract:
  The cross‐species transmission of viruses into new host populations, termed virus emergence, is a significant issue in public health, agriculture, wildlife management, and related fields. Virus emergence requires overlap between host populations, alterations in virus genetics to permit infection of new hosts, and adaptation to novel hosts such that between‐host transmission is sustainable, all of which are the purview of the fields of ecology and evolution. A firm understanding of the ecology of viruses and how they evolve is required for understanding how and why viruses emerge. In this paper, I address the evolutionary mechanisms of virus emergence and how they relate to virus ecology. I argue that, while virus acquisition of the ability to infect new hosts is not difficult, limited evolutionary trajectories to sustained virus between‐host transmission and the combined effects of mutational meltdown, bottlenecking, demographic stochasticity, density dependence, and genetic erosion in ecological sinks limit most emergence events to dead‐end spillover infections. Despite the relative rarity of pandemic emerging viruses, the potential of viruses to search evolutionary space and find means to spread epidemically and the consequences of pandemic viruses that do emerge necessitate sustained attention to virus research, surveillance, prophylaxis, and treatment.


id: cord-348819-gq7lp931
title: Dynamic and integrative approaches to understanding pathogen spillover
author: Becker, Daniel J.
date: 2019-08-12
txt: ./txt/cord-348819-gq7lp931.txt
cache: ./cache/cord-348819-gq7lp931.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1098/rstb.2019.0014
doi: 10.1098/rstb.2019.0014
abstract: nan
summary:
  The second set of manuscripts focuses on in-depth analysis of each of the factors affecting cross-species transmission: infection dynamics in reservoir hosts, pathogen survival in the environment, recipient host exposure, dose -response relationships and establishment of infection in recipient hosts. The authors show how modelling cross-species transmission as a percolation process, in which pathogens move from infected reservoirs to recipient hosts along a graph representing various spillover pathways [18, 19] , reveals first principles for how such datasets will behave and how common statistical tools can produce misleading inferences and poor predictions. This inclusive approach to confronting epidemiological models with longitudinal data in poorly understood reservoir host systems holds promise for elucidating spatio-temporal risk of pathogen spillover. Through several case studies (e.g. Lyme disease [63] , Hendra virus [64] , Plasmodium knowlesi [65] ), the authors further demonstrate how ecologically focused research has facilitated predicting spillover of particular pathogens in space and time and facilitated design of intervention strategies.


id: cord-348841-qxkmngyk
author: Kozakiewicz, Christopher P.
date: 2018-07-28
txt: ./txt/cord-348841-qxkmngyk.txt
cache: ./cache/cord-348841-qxkmngyk.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/30459828/
doi: 10.1111/eva.12678
summary:
  Our review emphasizes the expanding utility of landscape genetic methods available for elucidating key pathogen dynamics (particularly transmission and spread) and also how landscape genetic studies of pathogens can provide insight into host population dynamics. We excluded reviews (n = 15), meeting abstracts (n = 1), purely methods-based papers (n = 6) and articles that identified as or mentioned landscape genetics but did not sufficiently incorporate landscape factors or genetic data into the study (n = 32), studies that referred to any of our pathogen-related search terms without it being a primary motivation for the study (n = 21), and studies that used words like "transmit" or "parasite" outside of the context of infectious agents (such as the transmission of behaviours) (n = 6). Spatial variation in pathogen prevalence or infection risk can be represented in much the same way as any landscape variable , making spatial data relating to presence of an infectious agent well-suited for incorporation into host landscape genetic models.

title:
  Pathogens in space: Advancing understanding of pathogen dynamics and disease ecology through landscape genetics

abstract:
  Landscape genetics has provided many insights into how heterogeneous landscape features drive processes influencing spatial genetic variation in free‐living organisms. This rapidly developing field has focused heavily on vertebrates, and expansion of this scope to the study of infectious diseases holds great potential for landscape geneticists and disease ecologists alike. The potential application of landscape genetics to infectious agents has garnered attention at formative stages in the development of landscape genetics, but systematic examination is lacking. We comprehensively review how landscape genetics is being used to better understand pathogen dynamics. We characterize the field and evaluate the types of questions addressed, approaches used and systems studied. We also review the now established landscape genetic methods and their realized and potential applications to disease ecology. Lastly, we identify emerging frontiers in the landscape genetic study of infectious agents, including recent phylogeographic approaches and frameworks for studying complex multihost and host‐vector systems. Our review emphasizes the expanding utility of landscape genetic methods available for elucidating key pathogen dynamics (particularly transmission and spread) and also how landscape genetic studies of pathogens can provide insight into host population dynamics. Through this review, we convey how increasing awareness of the complementarity of landscape genetics and disease ecology among practitioners of each field promises to drive important cross‐disciplinary advances.


id: cord-349975-quw1gyw7
title: Extreme Competence: Keystone Hosts of Infections
author: Martin, Lynn B.
date: 2019-01-29
txt: ./txt/cord-349975-quw1gyw7.txt
cache: ./cache/cord-349975-quw1gyw7.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.tree.2018.12.009
doi: 10.1016/j.tree.2018.12.009
summary:
  Most prominent among these hosts are the superspreaders, but other forms of extreme competence (EC) exist and others await discovery; each with potentially strong but distinct implications for disease emergence and spread. So as to ground our framework in familiar territory, we collected data and plotted frequency distributions of all four aspects of host competence for two different infections: malaria parasites and lung nematodes ( Figure 1 ). Data from a wild tropical avian community suggest that most infections are chronic with most individuals maintaining parasite burdens insufficient for transmission to vectors (i.e., low suitability). In panel A, a malaria (vector) superattractor has high exposure risk, but it is unknown whether such hosts tend to have high or low suitability and transmissibility and thus act as superspreaders or superdiluters. Tolerance of infection: a role for animal behavior, potential immune mechanisms, and consequences for parasite transmission

abstract:
  Individual hosts differ extensively in their competence for parasites, but traditional research has discounted this variation, partly because modeling such heterogeneity is difficult. This discounting has diminished as tools have improved and recognition has grown that some hosts, the extremely competent, can have exceptional impacts on disease dynamics. Most prominent among these hosts are the superspreaders, but other forms of extreme competence (EC) exist and others await discovery; each with potentially strong but distinct implications for disease emergence and spread. Here, we propose a framework for the study and discovery of EC, suitable for different host–parasite systems, which we hope enhances our understanding of how parasites circulate and evolve in host communities.


id: cord-351490-2fx0w30u
title: Treatable traits and therapeutic targets: Goals for systems biology in infectious disease
author: Russell, Clark D.
date: 2017-04-27
txt: ./txt/cord-351490-2fx0w30u.txt
cache: ./cache/cord-351490-2fx0w30u.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.coisb.2017.04.003
doi: 10.1016/j.coisb.2017.04.003
summary:
  A systems medicine approach to infection has the potential to provide new solutions to old problems: to identify host traits that are potentially amenable to therapeutic intervention, and the host immune factors that could be targeted by host-directed therapies. We suggest there are two major goals for systems biology in infection medicine: (1) to identify subgroups of patients that share treatable features; and, (2) to integrate high-throughput data from clinical and in vitro sources in order to predict tractable therapeutic targets with the potential to alter disease trajectories for individual patients. A systems medicine approach to infection has the potential to combine and integrate relevant signals from clinical, genomic, transcriptomic, proteomic and pathogen biology data to draw inferences about disease pathogenesis. A more specific host-directed therapy, recombinant human activated protein C (rhAPC), was licensed for treatment of severe sepsis based on the results of a single clinical trial [20] .

abstract:
  Among the many medical applications of systems biology, we contend that infectious disease is one of the most important and tractable targets. We take the view that the complexity of the immune system is an inevitable consequence of its evolution, and this complexity has frustrated reductionist efforts to develop host-directed therapies for infection. However, since hosts vary widely in susceptibility and tolerance to infection, host-directed therapies are likely to be effective, by altering the biology of a susceptible host to induce a response more similar to a host who survives. Such therapies should exert minimal selection pressure on organisms, thus greatly decreasing the probability of pathogen resistance developing. A systems medicine approach to infection has the potential to provide new solutions to old problems: to identify host traits that are potentially amenable to therapeutic intervention, and the host immune factors that could be targeted by host-directed therapies. Furthermore, undiscovered sub-groups with different responses to treatment are almost certain to exist among patients presenting with life-threatening infection, since this population is markedly clinically heterogeneous. A major driving force behind high-throughput clinical phenotyping studies is the aspiration that these subgroups, hitherto opaque to observation, may be observed in the data generated by new technologies. Subgroups of patients are unlikely to be static – serial clinical and biological phenotyping may reveal different trajectories through the pathophysiology of disease, in which different therapeutic approaches are required. We suggest there are two major goals for systems biology in infection medicine: (1) to identify subgroups of patients that share treatable features; and, (2) to integrate high-throughput data from clinical and in vitro sources in order to predict tractable therapeutic targets with the potential to alter disease trajectories for individual patients.


id: cord-353609-no3mbg5d
title: An Ecological and Conservation Perspective on Advances in the Applied Virology of Zoonoses
author: Vandegrift, Kurt J.
date: 2011-04-15
txt: ./txt/cord-353609-no3mbg5d.txt
cache: ./cache/cord-353609-no3mbg5d.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3390/v3040379
doi: 10.3390/v3040379
summary:
  Conducting viral surveillance in animal reservoirs and invertebrate vectors can help explain circulation within host species; observed patterns of zoonotic transmission; and even allow for the prediction of periods of increased risk of zoonotic transmission (e.g., Rift valley fever and rainfall [25] ; West Nile virus (WNV) and American robin (Turdus turdus) migration [26] ; as well as hantavirus in mice [27, 28] ). Globalization, host ecology, host-virus dynamics, climate change, and anthropogenic landscape changes all contribute to the complexity of zoonotic viral emergence and disease, and create significant conservation and public health challenges. While the lasting efficacy of wildlife vaccination efforts has yet to be demonstrated with either endangered species or in breaking the transmission cycle of human pathogens, an increasing number of researchers are drawing attention to systems where it seems feasible [99, 103] ; demonstrating that intricate knowledge of host and virus ecology can greatly reduce the amount of vaccine coverage that is necessary to control these viruses.

abstract:
  The aim of this manuscript is to describe how modern advances in our knowledge of viruses and viral evolution can be applied to the fields of disease ecology and conservation. We review recent progress in virology and provide examples of how it is informing both empirical research in field ecology and applied conservation. We include a discussion of needed breakthroughs and ways to bridge communication gaps between the field and the lab. In an effort to foster this interdisciplinary effort, we have also included a table that lists the definitions of key terms. The importance of understanding the dynamics of zoonotic pathogens in their reservoir hosts is emphasized as a tool to both assess risk factors for spillover and to test hypotheses related to treatment and/or intervention strategies. In conclusion, we highlight the need for smart surveillance, viral discovery efforts and predictive modeling. A shift towards a predictive approach is necessary in today’s globalized society because, as the 2009 H1N1 pandemic demonstrated, identification post-emergence is often too late to prevent global spread. Integrating molecular virology and ecological techniques will allow for earlier recognition of potentially dangerous pathogens, ideally before they jump from wildlife reservoirs into human or livestock populations and cause serious public health or conservation issues.


id: cord-355024-v5lahyw4
title: Principles of Infectious Diseases: Transmission, Diagnosis, Prevention, and Control
author: van Seventer, Jean Maguire
date: 2016-10-24
txt: ./txt/cord-355024-v5lahyw4.txt
cache: ./cache/cord-355024-v5lahyw4.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/B9780128036785005166
doi: 10.1016/b978-0-12-803678-5.00516-6
summary:
  An infectious disease can be defined as an illness due to a pathogen or its toxic product, which arises through transmission from an infected person, an infected animal, or a contaminated inanimate object to a susceptible host. The outcome of exposure to an infectious agent depends, in part, upon multiple host factors that determine individual susceptibility to infection and disease. The goal of secondary prevention is to halt the progress of an infection during its early, often asymptomatic stages so as to prevent disease development or limit its severity; steps important for not only improving the prognosis of individual cases but also preventing infectious agent transmission. Broadly, public health efforts to control infectious diseases focus on primary and secondary prevention activities that reduce the potential for exposure to an infectious agent and increase host resistance to infection. A susceptible host is an individual who is at risk of infection and disease following exposure to an infectious agent.

abstract:
  Infectious disease control and prevention relies on a thorough understanding of the factors determining transmission. This article summarizes the fundamental principles of infectious disease transmission while highlighting many of the agent, host, and environmental determinants of these diseases that are of particular import to public health professionals. Basic principles of infectious disease diagnosis, control, and prevention are also reviewed.


id: cord-355239-fc52dn3v
title: The Role of Carbohydrates in Infection Strategies of Enteric Pathogens
author: Kato, Kentaro
date: 2014-11-15
txt: ./txt/cord-355239-fc52dn3v.txt
cache: ./cache/cord-355239-fc52dn3v.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.2149/tmh.2014-25
doi: 10.2149/tmh.2014-25
summary:
  In the case of Salmonella, the negative charge produced by sialic acid on the surface of the host cell is required as a non-specific adherence factor [11] . Individual fimbria recognize and bind to specific receptors to promote adhesion to the host cell surface [2, 12] . Type 1 fimbriae are highly expressed on the bacterial surface, allowing large quantities of bacteria to adhere via the FimH-Mannose interaction (Fig. 3 ). For example, the R64 plasmid, which encodes the pilV gene and engages in the adhesion of type 4 fimbriae, recognizes the di-saccharide moiety of bacterial surface polysaccharides (the core oligosaccharide or O-antigen unit of lipopolysaccharides, a unique structure of the bacterial cell surface) and determines the recipient bacteria of the conjugal transfer [26, 27] . Salmonella and assortative bacteria contain various adhesion factors, including several kinds of fimbriae, which contribute to bacterial virulence; however, analyses of their specific receptor moieties and functions are not yet complete [13, 15] .

abstract:
  Enteric pathogens cause considerable public health concerns worldwide including tropical regions. Here, we review the roles of carbohydrates in the infection strategies of various enteric pathogens including viruses, bacteria and protozoa, which infect the epithelial lining of the human and animal intestine. At host cell entry, enteric viruses, including norovirus, recognize mainly histo-blood group antigens. At the initial step of bacterial infections, carbohydrates also function as receptors for attachment. Here, we describe the function of carbohydrates in infection by Salmonella enterica and several bacterial species that produce a variety of fimbrial adhesions. During invasion by enteropathogenic protozoa, apicomplexan parasites utilize sialic acids or sulfated glycans. Carbohydrates serve as receptors for infection by these microbes; however, their usage of carbohydrates varies depending on the microbe. On the surface of the mucosal tissues of the gastrointestinal tract, various carbohydrate moieties are present and play a crucial role in infection, representing the site of infection or route of access for most microbes. During the infection and/or invasion process of the microbes, carbohydrates function as receptors for various microbes, but they can also function as a barrier to infection. One approach to develop effective prophylactic and therapeutic antimicrobial agents is to modify the drug structure. Another approach is to modify the mode of inhibition of infection depending on the individual pathogen by using and mimicking the interactions with carbohydrates. In addition, similarities in mode of infection may also be utilized. Our findings will be useful in the development of new drugs for the treatment of enteric pathogens.


