cord-000546-0hobwqpe	2011	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) .
cord-001714-jfawhnsq	2015	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) .
cord-002423-1u44tdrj	2017	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] ).
cord-003767-9xbu4hnq	2019	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 .
cord-003806-ctass7hz	2019	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.
cord-004914-cnz61qjy	2010	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.
cord-005281-wy0zk9p8	2017	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.
cord-007735-ejvv2lxv	2006	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.
cord-013837-x95r6bz8	2020	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.
cord-014397-7b88ycv8	1996	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.
cord-016717-2twm4hmc	2011	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.
cord-017008-c7skxte0	2014	
cord-017819-85x0juiw	2006	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.
cord-018425-vyiuv5qu	2017	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.
cord-018555-3lta1tbp	2016	
cord-018821-e9oxvgar	2016	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.
cord-019068-6j42euvc	2019	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.
cord-021465-2pj26fmv	2007	
cord-021552-6jbm869r	2007	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.
cord-026880-i45okohf	2020	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.
cord-029032-s9geepsc	2020	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] .
cord-031937-qhlatg84	2020	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 .
cord-048325-pk7pnmlo	2006	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.
cord-102383-m5ahicqb	2020	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.
cord-104317-t30dg6oj	2016	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.
cord-199630-2lmwnfda	2020	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.
cord-255181-du6rqc6i	2005	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.
cord-259505-7hiss0j3	2010	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.
cord-261466-b9r4cyp7	2014	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.
cord-262434-q4tk96tq	2014	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.
cord-262585-5vjqrnwh	2019	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.
cord-262682-gsvswr7v	2018	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
cord-263312-x7f0hn7f	2013	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
cord-264532-xfb94lq8	2008	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.
cord-264884-ydkigome	2008	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.
cord-269505-7g8lio9l	2010	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.
cord-269975-1ebmq7t8	2020	
cord-270604-u62437dh	2013	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).
cord-270803-jtv5jmkn	2011	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].
cord-276585-m1dkkbq7	2008	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).
cord-276637-re9c3e0b	2019	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 ).
cord-277417-f71jwdzj	2018	
cord-288231-vg8bwed9	2009	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.
cord-289443-46w52de3	2015	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) .
cord-290253-hxxizipk	2018	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) .
cord-290548-0wezrr1b	2020	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.
cord-291946-kq0rsuxj	2013	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.
cord-292657-gq3965se	2020	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.
cord-296179-hobh6akq	2012	(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.
cord-297960-4x1j0iqg	2019	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
cord-298475-3bhiattk	2020	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.
cord-299828-fb84rtmx	2013	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.
cord-305327-hayhbs5u	2017	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.
cord-307803-rlvk6bcx	2017	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.
cord-309642-wwaa6ls0	1986	
cord-312545-io2jmp7o	2011	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.
cord-313301-7mkadtp9	2007	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.
cord-314325-nquov2i0	2008	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.
cord-319448-gt6uqfrl	2003	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.
cord-319658-u0wjgw50	2017	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.
cord-320083-0k15w624	2020	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
cord-324697-c0dv1zmi	2020	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
cord-329149-1giy1fow	2017	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.
cord-330590-nu8ckeud	2018	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.
cord-335774-15fhg8o9	2020	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.
cord-337738-2qck1j1w	2020	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
cord-338804-nreqluol	2014	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.
cord-345157-fhmhpobi	2018	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] .
cord-345654-vyz6f3he	2016	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.
cord-348819-gq7lp931	2019	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.
cord-348841-qxkmngyk	2018	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.
cord-349975-quw1gyw7	2019	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
cord-351490-2fx0w30u	2017	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] .
cord-353609-no3mbg5d	2011	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.
cord-355024-v5lahyw4	2016	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.
cord-355239-fc52dn3v	2014	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] .