# ent

id: cord-010521-cpwl2ych
type: CELL_LINE
entity:
  cell lines PK 15 pig kidney SK 6 swine kidney and ST swine testicle A growth curve based on cytopathic effect CPE immunofluorescence IF hemadsorption Hads


id: cord-261446-ro1wm0kf
type: CELL_LINE
entity:
  PCV2 DNA negative pig pig No 2 Hepatitis E virus infections are a major cause of acute hepatitis in developing countries and because of the zoonotic transmission of HEV


id: cord-287538-qbf5lv7d
type: ORG
entity:
  the World Health Organization International Union of Immunologic Societies Allergen Nomenclature Committee


id: cord-287538-qbf5lv7d
type: ORG
entity:
  American Society of Anesthesiologists Committee on Occupational Health of Operating Room Personnel Latex


id: cord-322062-nnefbeo6
type: DNA
entity:
  u1111Jul1uuluI111u lll1uuuul1 11111 JUI I 11 b iu UUUU IU 1 11 P I UJ L IUIU I I UII I u UUULII ui uu Computer generated open reading frame


id: cord-321132-xdpb3ukt
type: DNA
entity:
  jit438 sha 82ad77b161e31fb733c63e3ebe5067c938d43d40 doc_id 321132 cord_uid xdpb3ukt Hepatitis E virus HEV


id: cord-329137-5pw07qje
type: WORK_OF_ART
entity:
  Immature and Mature Human Astrovirus Structure Conformational Changes and Similarities to Hepatitis E Virus


id: cord-318222-o9kc3x6z
type: DNA
entity:
  hepatitis E virus HEV nonstructural open reading frame 1 ORF1 Hepatitis C virus NS3 4A serine protease


id: cord-332046-ihc031ly
type: ORG
entity:
  the International Committee on Taxonomy of Viruses International Union of Microbiological Societies Molecular


id: cord-347244-abxv2mkz
type: SO
entity:
  ORF3 region forward primer HEVORF3 S 5 GGTGGTTTCTGGGGTGAC 3 reverse primer HEVORF3 AS 5 AGGGGTTGGTTGGATGAA 3 and probe


id: cord-347244-abxv2mkz
type: CHEMICAL
entity:
  Dordogne n 7 Finistère n 3 Deux Sèvres n 2 Loire Atlantique n 2 Haute Garonne n 1 Charentes n 1 Morbihan n 1 and Pyrénées Orientales n 1 Table 1 The number of


id: cord-351365-dc9t3vh3
type: RNA
entity:
  nascent viral RNA 72 73 However this mechanism is controversially discussed in literature 72 73 74 75


id: cord-351365-dc9t3vh3
type: CELL_TYPE
entity:
  human blood and L5178Y cells beta D ribofuranosyl 1 2 4 triazole 3 carboxamide A cytostatic agent Hepatitis E


id: cord-350964-0jtfc271
type: ORG
entity:
  Detection and Characterization of Homologues of Human Hepatitis Viruses and Pegiviruses in Rodents and Bats


id: cord-010092-uftc8inx
type: DNA
entity:
  ISBT date 2019 06 07 journal Vox Sang DOI 10 1111 vox 12792 sha 8255413c3d6cae0cd4a70c6000db8cc787837756 doc_id 10092 cord_uid uftc8inx nan


id: cord-010092-uftc8inx
type: DNA
entity:
  b globin ΤΝS9 3 55 the insulated b globin A1 TNS9 3 55and the oncogenic SFFV GFP vector Transduced cells


id: cord-010092-uftc8inx
type: PROTEIN
entity:
  heterozygous c 59T G and c 60A G p 20Leu Trp c 67A T p 23Thr Ser c 71A G and c 72G T p 24Glu Gly c 143C T s S c 208G T p 70Val Leu c 230C T p 77Thr Met


id: cord-010092-uftc8inx
type: PROTEIN
entity:
  AQP1 c 601delG CO 01N 06 mutation that induces the Co null phenotype Summary Conclusions The study provides a first overview on a number of different blood group alleles


id: cord-010092-uftc8inx
type: CL
entity:
  pRBC Summary Conclusions Atomic force microscopy in direct biophysics experiment allows to observe and to quantitatively measure the disturbances in the spectrin matrix


id: cord-010092-uftc8inx
type: CL
entity:
  allogeneic blood in breast cancer surgery is variable and differences of transfusion incidence have been observed in the literature Where the maximum surgical blood ordering schedule MSBOS dictates cross matching and reservation of blood before surgery factors deciding their utilization are varied and numerous Our hospital protocol guides that every patient planned for elective breast cancer surgery should routinely have a blood sample sent for reservation of one unit of compatible packed red blood cell


id: cord-010092-uftc8inx
type: GGP
entity:
  PFS HR 3 4 95 CI 1 9 6 3 P 0 001 for the whole study population and the TD RS subgroup HR 8 2 95 CI 3 4 21 0 P 0 001 In total 16 patients received iron chelation


id: cord-010092-uftc8inx
type: WORK_OF_ART
entity:
  HB CONTENT OF PACKED RED CELLS PRBC IS IT TIME TO LABEL EACH UNIT WITH HB CONTENT R Jain 1 N Marwaha 2 and S Sachdev 2 1 Transfusion Medicine Aiims New Delhi 2 Transfusion Medicine Pgimer Chandigarh India Background


id: cord-010092-uftc8inx
type: ORG
entity:
  N Deshpande Transfusion Medicine Tata Memorial Centre Homi Bhabha National Institute Mumbai India Background Red Blood Cell


id: cord-010092-uftc8inx
type: ORG
entity:
  Institute for Transfusion Medicine and Immunology Heidelberg University Medical Faculty Mannheim Mannheim Germany Background Rb


id: cord-010092-uftc8inx
type: ORG
entity:
  Leadership and Governance Cooperation and Collaboration Provision of Safe Blood and Blood Products Appropriate Clinical Use of Blood


id: cord-010092-uftc8inx
type: ORG
entity:
  Donor Selection Finance and Collection of Blood Bag Blood Collection Process Component Preparation Blood Testing and Blood Distribution


id: cord-010092-uftc8inx
type: EVENT
entity:
  Immunology and Transfusion Medicine Oslo University Hospital 2 Immunology University of Oslo Oslo 3 Immunology and Transfusion Medicine Akershus University


id: cord-010092-uftc8inx
type: WORK_OF_ART
entity:
  Interregional Blood Transfusion SRC Lausanne 2 Laboratory Diagnostics Interregional Blood Transfusion SRC Bern Switzerland Background


# bib

id: cord-000016-g9f6bdlp
title: WU Polyomavirus Infection in Children, Germany
author: Neske, Florian
date: 2008-04-17
txt: ./txt/cord-000016-g9f6bdlp.txt
cache: ./cache/cord-000016-g9f6bdlp.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2570908/
doi: 10.3201/eid0104.071325
abstract: nan
summary:
  During the study period, 1,326 NPA of hospitalized children with febrile respiratory tract diseases were received for viral diagnostic evaluation. In 34 (54.8%) of the WUPyV-positive samples, co-infections with other respiratory viruses were detected, most frequently with adenovirus (n = 10) and fl uA (n = 10), followed by hBoV (n = 9) and RSV (n = 5). In July 2002, Ministry of Health (MoH) and Médecins sans Frontières (MSF) teams working in the Begoua Commune Health Center, north of CAR''s capital Bangui, reported an increased number of patients from the Yembi I neighborhood who were showing signs of jaundice and extreme fatigue. Confi rmed cases were those in which patients'' serum samples were positive for HEV immunoglobulin (Ig) M or IgG. Of 715 suspected HEV case-patients recorded in the MSF hospital between July 22 and October 25, 2002, 552 (77%) lived in the Begoua commune (271 in the Yembi I neighborhood).


id: cord-002102-0zbp3uqf
author: Rasche, Andrea
date: 2016-07-17
txt: ./txt/cord-002102-0zbp3uqf.txt
cache: ./cache/cord-002102-0zbp3uqf.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4918144/
doi: 10.3201/eid2207.160168
summary:
  title: Hepatitis E Virus Infection in Dromedaries, North and East Africa, United Arab Emirates, and Pakistan, 1983–2015 A new hepatitis E virus (HEV-7) was recently found in dromedaries and 1 human from the United Arab Emirates. Recently, HEV sequences were reported from 3 dromedaries sampled in the United Arab Emirates (UAE) in 2013 and were classified as a new orthohepevirus A genotype, HEV-7 (2, 3) . To determine the geographic distribution of HEV-7, we conducted a geographically comprehensive study of HEV-7 prevalence in dromedaries by testing 2,438 specimens sampled in 6 countries during the past 3 decades. Serum and fecal samples were collected from dromedary camels in the UAE, Somalia, Sudan, Egypt, Kenya, and Pakistan during 1983-2015 (5-7). Detections of HEV-7 RNA in feces in this and a previous study (2) point at feces or feces-contaminated camel products, such as milk, as putative additional sources of human infection.

title:
  Hepatitis E Virus Infection in Dromedaries, North and East Africa, United Arab Emirates, and Pakistan, 1983–2015

abstract:
  A new hepatitis E virus (HEV-7) was recently found in dromedaries and 1 human from the United Arab Emirates. We screened 2,438 dromedary samples from Pakistan, the United Arab Emirates, and 4 African countries. HEV-7 is long established, diversified and geographically widespread. Dromedaries may constitute a neglected source of zoonotic HEV infections.


id: cord-002589-xq3iq8ai
author: Frossard, Jean-Pierre
date: 2017-06-09
txt: ./txt/cord-002589-xq3iq8ai.txt
cache: ./cache/cord-002589-xq3iq8ai.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5490802/
doi: 10.3390/v9060110
summary:
  To follow up these studies, we report here on (1) the investigation of PRRSV active infection (RNA in tonsil) using the same 2013 abattoir survey sample-set and (2) an analysis of the correlation of PRRSV and HEV infection in these pigs, which could be of significance for the control of both diseases and in informing farming practices for reducing HEV in the food chain. The phylogenetic trees (Figure 1 ) illustrate the genetic diversity of the ORF5 genes from the 23 samples in this study in comparison to the vaccine virus licensed in the UK at the time and 48 published reference sequences representing the different genotypes and subtypes ( Figure 1A ) and in more detail, in the context of 431 previously sequenced viruses specifically from UK pigs between 1991 and 2014 (unpublished data) ( Figure 1B ).

title:
  UK Pigs at the Time of Slaughter: Investigation into the Correlation of Infection with PRRSV and HEV

abstract:
  Hepatitis E virus (HEV) and porcine reproductive and respiratory syndrome virus (PRRSV) and are both globally prevalent in the pig population. While HEV does not cause clinical disease in pigs, its zoonotic potential has raised concerns in the food safety sector. PRRS has become endemic in the United Kingdom (UK) since its introduction in 1991, and continues to cause considerable economic losses to the swine industry. A better understanding of the current prevalence and diversity of PRRSV and HEV in the UK, and their potential association, is needed to assess risks and target control measures appropriately. This study used plasma, tonsil, and cecal content samples previously collected from pigs in 14 abattoirs in England and Northern Ireland to study the prevalence of several pathogens including PRRSV and HEV. The diversity of PRRSV strains detected in these samples was analyzed by sequencing open reading frame 5 (ORF5), revealing no substantial difference in PRRSV strains from these clinically unaffected pigs relative to those from clinical cases of disease in the UK. Despite the potential immuno-modulatory effect of PRRSV infection, previously demonstrated to affect Salmonella and HEV shedding profiles, no significant association was found between positive PRRSV status and positive HEV status.


id: cord-003787-hfnht8wa
title: Hepatitis E in southern Vietnam: Seroepidemiology in humans and molecular epidemiology in pigs
author: Berto, A.
date: 2018-02-01
txt: ./txt/cord-003787-hfnht8wa.txt
cache: ./cache/cord-003787-hfnht8wa.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6645987/
doi: 10.1111/zph.12364
summary:
  We found a high prevalence of HEV GT3 viral RNA in pigs (19.1% in faecal samples and 8.2% in rectal swabs) and a high HEV seroprevalence in pig farmers (16.0%) and a hospital-attending population (31.7%) in southern Vietnam. Hypothesising that HEV GT3 and GT4 are common zoonotic pathogens in Vietnam, we aimed to estimate (i) the HEV seroprevalence in a hospital-attending population, as a proxy for the general population, (ii) the HEV seroprevalence in individuals working in close contact with pigs (farmers, family members of farmers, animal workers, veterinarians and abattoir workers) and (iii) the prevalence of HEV infection in pigs. Although the seroprevalence in both populations increased with age, the prevalence of anti-HEV IgG was higher in children in the hospital population than in children enrolled in the farm cohort study (Figure 3 ). This study aimed to measure the prevalence of faecal HEV shedding on pig farms and the seroprevalence of HEV in the human population in southern Vietnam (Dong Thap province).

abstract:
  Viral pathogens account for a significant proportion of the burden of emerging infectious diseases in humans. The Wellcome Trust-Vietnamese Initiative on Zoonotic Infections (WT-VIZIONS) is aiming to understand the circulation of viral zoonotic pathogens in animals that pose a potential risk to human health. Evidence suggests that human exposure and infections with hepatitis E virus (HEV) genotypes (GT) 3 and 4 results from zoonotic transmission. Hypothesising that HEV GT3 and GT4 are circulating in the Vietnamese pig population and can be transmitted to humans, we aimed to estimate the seroprevalence of HEV exposure in a population of farmers and the general population. We additionally performed sequence analysis of HEV in pig populations in the same region to address knowledge gaps regarding HEV circulation and to evaluate if pigs were a potential source of HEV exposure. We found a high prevalence of HEV GT3 viral RNA in pigs (19.1% in faecal samples and 8.2% in rectal swabs) and a high HEV seroprevalence in pig farmers (16.0%) and a hospital-attending population (31.7%) in southern Vietnam. The hospital population was recruited as a general-population proxy even though this particular population subgroup may introduce bias. The detection of HEV RNA in pigs indicates that HEV may be a zoonotic disease risk in this location, although a larger sample size is required to infer an association between HEV positivity in pigs and seroprevalence in humans.


id: cord-003961-gs75ebo4
title: Hepatitis E Virus Entry
author: Yin, Xin
date: 2019-09-20
txt: ./txt/cord-003961-gs75ebo4.txt
cache: ./cache/cord-003961-gs75ebo4.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6832200/
doi: 10.3390/v11100883
summary:
  The enteric route of transmission, EM evidence of naked virions in the feces, and the lack of coding capacity for envelope proteins all suggest that HEV is a nonenveloped virus. The enteric route of transmission, EM evidence of naked virions in the feces, and the lack of coding capacity for envelope proteins all suggest that HEV is a nonenveloped virus. However, recent studies show that the virus released from infected cells and circulating in the blood adopts a membrane associated, "quasienveloped" form, named "eHEV" [10, 11, 22] (Figure 1b ). However, recent studies show that the virus released from infected cells and circulating in the blood adopts a membrane associated, "quasienveloped" form, named "eHEV" [10, 11, 22] (Figure 1b ). The available evidence suggests that naked and quasienveloped HEV particles use different mechanisms for cell entry, and that entry of eHEV requires lysosomal degradation of the viral membrane. ORF3 protein of hepatitis E virus is essential for virion release from infected cells

abstract:
  Hepatitis E virus (HEV) infection is a major cause of acute hepatitis worldwide. It is transmitted enterically but replicates in the liver. Recent studies indicate that HEV exists in two forms: naked, nonenveloped virions that are shed into feces to mediate inter-host transmission, and membrane-cloaked, quasienveloped virions that circulate in the bloodstream to mediate virus spread within a host. Both virion types are infectious, but differ in the way they infect cells. Elucidating the entry mechanism for both virion types is essential to understand HEV biology and pathogenesis, and is relevant to the development of treatments and preventions for HEV. This review summarizes the current understanding of the cell entry mechanism for these two HEV virion types.


id: cord-010092-uftc8inx
title: Abstract of 29th Regional Congress of the ISBT
author: nan
date: 2019-06-07
txt: ./txt/cord-010092-uftc8inx.txt
cache: ./cache/cord-010092-uftc8inx.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169345/
doi: 10.1111/vox.12792
abstract: nan
summary:
  Prospective testing of blood donations in endemic areas of the U.S. revealed 0.38% of donors were positive for Babesia DNA or antibodies (Moritz, NEJM, 2016) Aims: -To report results of ongoing Babesia clinical trial -To explain significance of Babesia as a TT infection Methods: In cobas â Babesia for use on the cobas â 6800/8800 Systems, is a qualitative polymerase chain reaction nucleic acid amplification test, developed to detect in whole blood (WB) donor samples the 4 Babesia species that cause human disease: B. In sensitivity analyses, there were two discrepant results for HIV testing, three for HCV, and five for anti-HBc. Summary/Conclusions: Elecsys â infectious disease parameters on the cobas e 801 analyser demonstrate high specificity/sensitivity for screening first-time blood donor samples, with similar clinical performance to other commercially available assays.


id: cord-010521-cpwl2ych
title: Propagation of Hemagglutinating Encephalomyelitis Virus in Porcine Cell Cultures
author: Andries, K.
date: 2010-05-13
txt: ./txt/cord-010521-cpwl2ych.txt
cache: ./cache/cord-010521-cpwl2ych.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7194162/
doi: 10.1111/j.1439-0450.1980.tb01693.x
summary:
  SUMMARY: This study reports some cultural characteristics of the VW 572 strain of hemagglutinating encephalomyelitis virus (HEV) in primary pig kidney (PPK) cells, primary pig testicle (PPT) cells, secondary pig thyroid (SPTh) cells and the cell lines PK‐15 (pig kidney), SK−6 (swine kidney) and ST (swine testicle). A growth curve of HEV was prepared with the cell culture virus stock inoculated on SPTh, PPK, PK-15, SK-6, PPT and PT cells. A growth curve, based on cytopathic effect (CPE), immunofluorescence (IF), hemadsorption (Hads) and hemagglutination (HA), showed that SPTh and PPK cells were most susceptible for cultivation and quantitation of the virus. A growth curve, based on cytopathic effect (CPE), immunofluorescence (IF), hemadsorption (Hads) and hemagglutination (HA), showed that SPTh and PPK cells were most susceptible for cultivation and quantitation of the virus.

abstract:
  SUMMARY: This study reports some cultural characteristics of the VW 572 strain of hemagglutinating encephalomyelitis virus (HEV) in primary pig kidney (PPK) cells, primary pig testicle (PPT) cells, secondary pig thyroid (SPTh) cells and the cell lines PK‐15 (pig kidney), SK−6 (swine kidney) and ST (swine testicle). A growth curve, based on cytopathic effect (CPE), immunofluorescence (IF), hemadsorption (Hads) and hemagglutination (HA), showed that SPTh and PPK cells were most susceptible for cultivation and quantitation of the virus. For the detection of replication in tubes inoculated with small amounts of virus, CPE, Hads and HA appeared to be useful and sensitive criteria. Repeated virus quantitation trials revealed a high variation in titration end‐points, even in the most susceptible cell types. The optimal procedure for the isolation of HEV from clinical specimens is preferably to inoculate the material on SPTh or PPK cells and to make a blind passage if the HA test at 7 days post inoculation is negative. ZUSAMMENFASSUNG: Züchtung von Hemagglutinating Encephalomyelitis Virus (HEV) in porcinen Zellkulturen Kulturelle Eigenschaften des HEV‐Stammes VW 572 in primären Schweinenierenzellen (PPK), primären Schweinehodenzellen (PPT), sekundären Schweineschilddrüsenzellen (SPTh) und in den Zellinien PK‐15 (Schweinenieren), SK−6 (Schweinenieren) und ST (Schweinehoden) werden beschrieben. Vermehrungskurven, die mit Hilfe des cytopatischen Effektes (CPE), der Immunofluoreszenz (IF), der Hämadsorption (Hads) und der Hämagglutination als Kriterien für die Virusreplikation erstellt wurden, zeigten, daß SPTh und PPK‐Zellen am empfindlichsten für die Züchtung und Titration des Virus sind. Zum Nachweis der Virusvermehrung in Röhrchen, die mit kleinen Virusmengen beimpft wurden, waren CPE, Hads und HA empfindliche und brauchbare Kriterien. Wiederholte Virustitrationen zeigten eine hohe Variation der Titerendpunkte auch in hochempfänglichen Zellkulturen. Die optimale Methode für die Isolierung von HEV von klinischem Material ist die Verimpfung auf SPTh oder PPK mit anschließender Blindpassage, wenn der HA‐Test sieben Tage p. inf. negativ ist. RÉSUMÉ: Culture du virus hémagglutinant de l'encéphalomyélite (HEV) dans des cultures de cellules de porc On décrit les propriétés de culture de la souche HEV VW 572 dans des cellules primaires de reins de pores (PPK), dans des cellules primaires de testicules de porcs (PPT), dans des cellules secondaires de glandes tyroïdes de porcs (SPTh) et dans les lignées cellulaires PK‐15 (reins de porcs), SK−6 (reins de porcs) et ST (testicules de porcs). Les courbes de multiplication établies avec l'effet cytopathique (CPE), l'immunofluorescence (IF), l'hémadsorption (Hads) et l'hémagglutination (HA) comme critères pour la réplication du virus ont montré que les cellules SPTh et PPK étaient les plus sensibles pour la culture et la titration du virus. CPE, Hads et HA furent les critères sensibles et utilisables pour la mise en évidence de la multiplication virale en tubes inoculés avec de petites quantités de virus. Des titrations du virus répétées ont montré une forte variation du titre final également dans les cultures cellulaires hautement réceptrices. La méthode optimale pour l'isolement de HEV à partir d'un matériel clinique est l'inoculation sur SPTh ou PPK avec passages à l'aveugle si le test HA est négatif 7 jours après l'infection. RESUMEN: Propagación del virus hemoaglutinante de la encefalomielitis (HEV) en los cultivos de células de cerdos Se describen las propiedades culturales de la estirpe HEV VW 572 en células renales primarias de cerdo (PPK), células testiculares primarias de cerdo, células tiroideas secundarias de cerdo (SPTh) y en las líneas celulares PK‐15 (riñones de cerdo), SK−6 (riñones porcinos) y ST (testículos de cerdo). Las curvas de multiplicación, las cuales se establecieron con ayuda del efecto citopático (CPE), la inmunofluorescencia (IF), la hemoadsorción (Hads) y la hemoaglutinación como criterios para la replicación virósica, mostraban que las células SPTh y PPK son las más sensibles para el cultivo y titulación del virus. Para la puesta en evidencia de la multiplicación virósica en tubitos, los cuales se inocularon con cantidades pequeñas de virus, eran CPE, Hads y HA criterios sensibles y útiles. Titulaciones repetidas de virus mostraban una variación elevada de los puntos finales de títulos incluso en cultivos celulares harto receptibles. El método óptimo para el aislamiento de HEV a partir de material clínico consiste en la inoculación a SPTH o PPK con pase ciego inmediato si la prueba HA es negativa 7 días después de la infección.


id: cord-253501-hkxlq3os
title: Recent Advances Towards the Development of a Potent Antiviral Against the Hepatitis E Virus
author: Anang, Saumya
date: 2018-06-28
txt: ./txt/cord-253501-hkxlq3os.txt
cache: ./cache/cord-253501-hkxlq3os.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.14218/jcth.2018.00005
doi: 10.14218/jcth.2018.00005
summary:
  [29] [30] [31] [32] Ribavirin inhibits host inosine monophosphate dehydrogenase, thereby depleting cellular GTP pools and blocking viral replication during HEV infection. Sofosbuvir, a prodrug of a uridine nucleoside analogue that acts as a direct-acting antiviral against hepatitis C virus (HCV) RNA-dependent RNA polymerase in its active form, was reported by Dao Thi et al. 63, 64 Zinc salts were shown to block the replication of both genotype 1 and genotype 3 HEV by inhibiting the activity of viral RNA-dependent RNA polymerase in cultured human hepatoma cells. Zinc directly inhibits HEV RNA-dependent RNA polymerase activity in vitro and displays moderate cooperativity with ribavirin in inhibiting viral replication in mammalian cell culture models of HEV infection. Ribavirin therapy inhibits viral replication on patients with chronic hepatitis e virus infection Zinc salts block hepatitis E virus replication by inhibiting the activity of viral RNA-dependent RNA polymerase

abstract:
  Hepatitis E virus (HEV) is one of the leading causes of acute viral hepatitis. It also causes acute liver failure and acute-on-chronic liver failure in many patients, such as those suffering from other infections/liver injuries or organ transplant/chemotherapy recipients. Despite widespread sporadic and epidemic incidents, there is no specific treatment against HEV, justifying an urgent need for developing a potent antiviral against it. This review summarizes the known antiviral candidates and provides an overview of the potential targets for the development of specific antivirals against HEV.


id: cord-258327-03vk6enj
author: Schultze, Beate
date: 1991-01-31
txt: ./txt/cord-258327-03vk6enj.txt
cache: ./cache/cord-258327-03vk6enj.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/0042682291900268
doi: 10.1016/0042-6822(91)90026-8
summary:
  The purified HE protein retained acetylesterase activity and was able to function as a receptor-destroying enzyme rendering red blood cells resistant against agglutination by both coronaviruses. However, it was found to recognize glycoconjugates containing N-acetyl-9-O-acetylneuraminic acid as indicated by a binding assay with rat serum proteins blotted to nitrocellulose and by its ability to inhibit the hemagglutinating activity of BCV, HEV, and influenza C virus. The virus pellet was resuspended in PBS and used for (i) analysis by polyacrylamide gel electrophoresis ; (ii) determination of the esterase activity ; (iii) hemagglutination and hemagglutination-inhibition assays ; and (iv) purification of the viral glycoproteins . These erythrocytes and control cells, which had been incubated with PBS, were used to determine the HA titer of BCV, HEV, and influenza C virus . As shown in Table 1 , incubation of erythrocytes with purified acetylesterase from either BCV or HEV rendered the cells resistant to agglutination by both coronaviruses as well as by influenza C virus .

title:
  Isolated HE-protein from hemagglutinating encephalomyelitis virus and bovine coronavirus has receptor-destroying and receptor-binding activity

abstract:
  Abstract Bovine coronavirus (BCV) and hemagglutinating encephalomyelitis virus (HEV) from swine were found to grow to high titers in MDCK I cells, a subline of Madin Darby canine kidney cells. Virus grown in these cells was used to isolate and purify the HE-protein. This protein has been shown recently to have acetylesterase activity and to function as the receptor-destroying enzyme of BCV. Here we show that HEV contains this enzyme, too. The glycoproteins were solubilized by treatment of virions with octylglucoside. Following centrifugation through a sucrose gradient the surface proteins S and HE (hemagglutinin-esterase) were obtained in purified form. After removal of the detergent by dialysis, HE formed rosettes as shown by electron microscopy. The purified HE protein retained acetylesterase activity and was able to function as a receptor-destroying enzyme rendering red blood cells resistant against agglutination by both coronaviruses. HE protein released from the viral membrane failed to agglutinate red blood cells. However, it was found to recognize glycoconjugates containing N-acetyl-9-O-acetylneuraminic acid as indicated by a binding assay with rat serum proteins blotted to nitrocellulose and by its ability to inhibit the hemagglutinating activity of BCV, HEV, and influenza C virus. The purified enzyme provides a useful tool for analyzing the cellular receptors for coronaviruses.


id: cord-261446-ro1wm0kf
author: Yang, Yifei
date: 2015-03-26
txt: ./txt/cord-261446-ro1wm0kf.txt
cache: ./cache/cord-261446-ro1wm0kf.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/25889526/
doi: 10.1186/s12917-015-0375-z
summary:
  CASE PRESENTATION: In this study, we characterized the HEV and PCV2 co-infection in 2–3 month-old piglets, based on pathogen identification and the pathological changes observed, in Hebei Province, China. PCR was used to identify the pathogen and we tested for eight viruses (HEV, Porcine reproductive and respiratory syndrome virus, PCV2, Classical swine fever virus, Porcine epidemic diarrhea virus, Transmissible gastroenteritis coronavirus, Porcine parvovirus and Pseudorabies virus) that are prevalent in Chinese pig farms. CONCLUSION: HEV and PCV2 co-infection in piglets was detected in four out of seven dead pigs from two pig farms in Hebei, China, producing severe pathological changes. In the present study, pathogen identification and the observation of pathological changes demonstrated a natural co-infection with HEV and PCV2 in the swine on two pig farms in Hebei Province, China. The lesions observed in the lung, liver, heart, kidney, lymph node, spleen and intestinal tract tissues were similar in all the pigs necropsied.

title:
  Fatal disease associated with Swine Hepatitis E virus and Porcine circovirus 2 co-infection in four weaned pigs in China

abstract:
  BACKGROUND: In recent decades, Porcine circovirus 2 (PCV2) infection has been recognized as the causative agent of postweaning multisystemic wasting syndrome, and has become a threat to the swine industry. Hepatitis E virus (HEV) is another high prevalent pathogen in swine in many regions of the world. PCV2 and HEV are both highly prevalent in pig farms in China. CASE PRESENTATION: In this study, we characterized the HEV and PCV2 co-infection in 2–3 month-old piglets, based on pathogen identification and the pathological changes observed, in Hebei Province, China. The pathological changes were severe, and general hyperemia, hemorrhage, inflammatory cell infiltration, and necrosis were evident in the tissues of dead swine. PCR was used to identify the pathogen and we tested for eight viruses (HEV, Porcine reproductive and respiratory syndrome virus, PCV2, Classical swine fever virus, Porcine epidemic diarrhea virus, Transmissible gastroenteritis coronavirus, Porcine parvovirus and Pseudorabies virus) that are prevalent in Chinese pig farms. The livers, kidneys, spleens, and other organs of the necropsied swine were positive for HEV and/or PCV2. Immunohistochemical staining showed HEV- and PCV2-antigen-positive signals in the livers, kidneys, lungs, lymph nodes, and intestine. CONCLUSION: HEV and PCV2 co-infection in piglets was detected in four out of seven dead pigs from two pig farms in Hebei, China, producing severe pathological changes. The natural co-infection of HEV and PCV2 in pigs in China has rarely been reported. We speculate that co-infection with PCV2 and HEV may bring some negative effect on pig production and recommend that more attention should be paid to this phenomenon.


id: cord-261925-nsq837z1
title: Preventing transfer of infectious agents
author: Denner, Joachim
date: 2015-08-24
txt: ./txt/cord-261925-nsq837z1.txt
cache: ./cache/cord-261925-nsq837z1.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.ijsu.2015.08.032
doi: 10.1016/j.ijsu.2015.08.032
summary:
  Xenotransplantation using pig cells, tissues and organs may be associated with the transfer of porcine infectious agents, which may infect the human recipient and in the worst case induce a disease (zoonosis). To prevent this, a broad screening program of the donor animals for putative zoonotic microorganisms, including bacteria, viruses, fungi and others, using sensitive and specific detection methods has to be performed. In the case of porcine endogenous retroviruses (PERVs) which are integrated in the genome of all pigs and which cannot be eliminated this way, selection of animals with low virus expression and generation of genetically modified pigs suppressing PERV expressions may be performed. At the moment hepatitis E virus (HEV), porcine cytomegalovirus (PCMV), porcine circoviruses (PCV), porcine lymphotropic herpes viruses (PLHV), and porcine endogenous retroviruses (PERVs) are thought to pose the main risk for reasons to be discussed below and therefore these microorganisms will be analysed in the next chapters in more details.

abstract:
  Xenotransplantation using pig cells, tissues and organs may be associated with the transfer of porcine infectious agents, which may infect the human recipient and in the worst case induce a disease (zoonosis). To prevent this, a broad screening program of the donor animals for putative zoonotic microorganisms, including bacteria, viruses, fungi and others, using sensitive and specific detection methods has to be performed. As long as it is still unknown, which microorganism represents a real risk for the recipient, experience from allotransplantation should be brought in. Due to the fact that pigs can be screened long before the date of transplantation, xenotransplantation will become eventually safer compared with allotransplantation. Screening and selection of animals free of potential zoonotic microorganisms, Caesarean section, vaccination and/or treatment with chemotherapeutics are the strategies of choice to obtain donor animals not transmitting microorganisms. In the case of porcine endogenous retroviruses (PERVs) which are integrated in the genome of all pigs and which cannot be eliminated this way, selection of animals with low virus expression and generation of genetically modified pigs suppressing PERV expressions may be performed.


id: cord-267015-mprsdi2e
author: Zhu, Zhongyu
date: 2008-03-15
txt: ./txt/cord-267015-mprsdi2e.txt
cache: ./cache/cord-267015-mprsdi2e.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/18271743/
doi: 10.1086/528801
summary:
  One of these antibodies, m102, which exhibited the highest level of cross-reactive neutralization of both NiV and HeV G, was affinity maturated by light-chain shuffling combined with random mutagenesis of its heavy-chain variable domain and panning against sG(HeV). We have previously identified neutralizing human monoclonal antibodies against Nipah virus (NiV) and Hendra virus (HeV) by panning a large nonimmune antibody library against a soluble form of the HeV attachment-envelope glycoprotein G (sG HeV ). One of these antibodies, m102, which exhibited the highest level of cross-reactive neutralization of both NiV and HeV G, was affinity maturated by light-chain shuffling combined with random mutagenesis of its heavychain variable domain and panning against sG HeV . To demonstrate that m102.4 measured in plasma was biologically active, serum collected on days 1, 4, and 8 was evaluated using virus neutralization assays, as described above (data not shown). Receptor binding, fusion inhibition, and induction of cross-reactive neutralizing antibodies by a soluble G glycoprotein of Hendra virus

title:
  Exceptionally Potent Cross-Reactive Neutralization of Nipah and Hendra Viruses by a Human Monoclonal Antibody

abstract:
  We have previously identified neutralizing human monoclonal antibodies against Nipah virus (NiV) and Hendra virus (HeV) by panning a large nonimmune antibody library against a soluble form of the HeV attachment-envelope glycoprotein G (sG(HeV)). One of these antibodies, m102, which exhibited the highest level of cross-reactive neutralization of both NiV and HeV G, was affinity maturated by light-chain shuffling combined with random mutagenesis of its heavy-chain variable domain and panning against sG(HeV). One of the selected antibody Fab clones, m102.4, had affinity of binding to sG(HeV) that was equal to or higher than that of the other Fabs; it was converted to IgG1 and tested against infectious NiV and HeV. It exhibited exceptionally potent and cross-reactive inhibitory activity with 50% inhibitory concentrations below 0.04 and 0.6 μg/mL, respectively. The virus-neutralizing activity correlated with the binding affinity of the antibody to sG(HeV) and sG(NiV). m102.4 bound a soluble form of NiV G (sG(NiV)) better than it bound sG(HeV), and it neutralized NiV better than HeV, despite being originally selected against sG(HeV). These results suggest that m102.4 has potential as a therapeutic agent for the treatment of diseases caused by henipaviruses. It could be also used for prophylaxis and diagnosis, and as a research reagent


id: cord-277159-klhmed21
author: Bassal, R.
date: 2019-02-22
txt: ./txt/cord-277159-klhmed21.txt
cache: ./cache/cord-277159-klhmed21.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1017/s0950268819000062
doi: 10.1017/s0950268819000062
summary:
  Human HEV infection, investigated using seroprevalence studies, was found to be more prevalent in older ages [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] , lower socio-economic status [21] , poorer residence areas [9, [14] [15] , among sheltered homeless adults [22] or uneducated people [14] , specific nationalities (for example, higher in mixed race donors and ethnic groups within China [12, 15] , or in immigrants from Afghanistan [14] ), drinking water from wells or rivers [15] , consumption of meat products [7, 15, 17, 23] especially pork [24, 25] and following blood transfusions [1] . This study aimed to assess HEV seroprevalence in camels (dromedary), in Bedouins living in the southern part of Israel in the vicinity of camels, in non-Bedouins Arabs (Muslims living in northern and central Israel) and in Israeli-born Jews and to assess the factors associated with anti-HEV seropositivity.

title:
  Seroprevalence of hepatitis E virus in dromedary camels, Bedouins, Muslim Arabs and Jews in Israel, 2009–2017

abstract:
  Hepatitis E virus (HEV) is an emerging cause of viral hepatitis worldwide. Recently, HEV-7 has been shown to infect camels and humans. We studied HEV seroprevalence in dromedary camels and among Bedouins, Arabs (Muslims, none-Bedouins) and Jews and assessed factors associated with anti-HEV seropositivity. Serum samples from dromedary camels (n = 86) were used to determine camel anti-HEV IgG and HEV RNA positivity. Human samples collected between 2009 and 2016 from >20 years old Bedouins (n = 305), non-Bedouin Arabs (n = 320) and Jews (n = 195), were randomly selected using an age-stratified sampling design. Human HEV IgG levels were determined using Wantai IgG ELISA assay. Of the samples obtained from camels, 68.6% were anti-HEV positive. Among the human populations, Bedouins and non-Bedouin Arabs had a significantly higher prevalence of HEV antibodies (21.6% and 15.0%, respectively) compared with the Jewish population (3.1%). Seropositivity increased significantly with age in all human populations, reaching 47.6% and 34.8% among ⩾40 years old, in Bedouins and non-Bedouin Arabs, respectively. The high seropositivity in camels and in ⩾40 years old Bedouins and non-Bedouin Arabs suggests that HEV is endemic in Israel. The low HEV seroprevalence in Jews could be attributed to higher socio-economic status.


id: cord-285935-5rsk6g7l
title: Hepatitis E Virus Drug Development
author: Kinast, Volker
date: 2019-05-28
txt: ./txt/cord-285935-5rsk6g7l.txt
cache: ./cache/cord-285935-5rsk6g7l.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3390/v11060485
doi: 10.3390/v11060485
summary:
  Cyclic peptides (CP) that had been developed to abrogate interaction of p6Gag and TSG101 and inhibited viral release of HIV Virus like particles (VLPs) [76] were tested for their activity against HEV [77] . The compounds RBV and mycophenolic acid (MPA), both of which target enzymes involved in nucleotide synthesis, are either already used as treatment against HEV or have been reported for their potential to inhibit the virus. So far, the antiviral activity against HEV of only four drugs (Sofosbuvir, pegIFN-α, Ribavirin and silvestrol) was approved in experimental settings beyond in vitro cell culture systems. Sofosbuvir Inhibits Hepatitis E Virus Replication In Vitro and Results in an Additive Effect When Combined With Ribavirin Sofosbuvir shows antiviral activity in a patient with chronic hepatitis E virus infection Zinc Salts Block Hepatitis E Virus Replication by Inhibiting the Activity of Viral RNA-Dependent RNA Polymerase The natural compound silvestrol inhibits hepatitis E virus (HEV) replication in vitro and in vivo

abstract:
  Hepatitis E virus (HEV) is an underestimated disease, leading to estimated 20 million infections and up to 70,000 deaths annually. Infections are mostly asymptomatic but can reach mortality rates up to 25% in pregnant women or become chronic in immunocompromised patients. The current therapy options are limited to the unspecific antivirals Ribavirin (RBV) and pegylated Interferon-α (pegIFN-α). RBV leads to viral clearance in only 80% of patients treated, and is, similar to pegIFN-α, contraindicated in the major risk group of pregnant women, emphasizing the importance of new therapy options. In this review, we focus on the urgent need and current efforts in HEV drug development. We provide an overview of the current status of HEV antiviral research. Furthermore, we discuss strategies for drug development and the limitations of the approaches with respect to HEV.


id: cord-287538-qbf5lv7d
title: Latex Allergy: Current Status and Future Perspectives
author: Nucera, Eleonora
date: 2020-09-28
txt: ./txt/cord-287538-qbf5lv7d.txt
cache: ./cache/cord-287538-qbf5lv7d.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.2147/jaa.s242058
doi: 10.2147/jaa.s242058
summary:
  The following eligibility criteria were used for article inclusion: population: patients with latex allergy and/or at risk for anaphylaxis; intervention: any approaches or protocols that incorporated a strategy for latex allergy and anaphylaxis management; comparator: any studies irrespective of whether there was a comparator included in the study design; outcomes: any related to prevalence, diagnostics, and treatments including primary prevention and immunotherapy; and study design: experimental studies and observational studies. 65 On the other hand, only a small case series of nine patients has described the efficacy of accelerator-free medical gloves in the secondary prevention of allergic contact dermatitis (ACD) caused by rubber accelerators in HCWs. 66 Gentili et al 67 showed that an effective and exemplary example of secondary prevention of latex allergy is feasible for infants born with spina bifida.

abstract:
  Allergy to natural rubber latex (NRLA) from Hevea brasiliensis is a relevant public health issue, in particular in healthcare workers and groups at risk. Clinical manifestations of NRLA can range from mild skin disorders to life-threatening systemic reactions. Prevention measures remain the gold-standard treatment for patients suffering from NRLA, but the only etiological therapy able to influence the natural history of NRLA is specific desensitization. This review aims to underline the epidemiological, clinical and diagnostic aspects of NRLA, and carries out a complete and wide-ranging review of the current literature on NRLA management and immunotherapy.


id: cord-290136-n3irdy0x
title: Emerging zoonotic viral infections of occupational health importance
author: Vonesch, Nicoletta
date: 2019-03-27
txt: ./txt/cord-290136-n3irdy0x.txt
cache: ./cache/cord-290136-n3irdy0x.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1093/femspd/ftz018
doi: 10.1093/femspd/ftz018
summary:
  West Nile Virus (WNV) disease, Crimean-Congo Hemorrhagic Fever (CCHF) disease and Hepatitis E virus (HEV) infection were included in the review for their potential zoonotic transmission. Examples of zoonotic virus of other origin include West Nile Virus (WNV), Chikungunya virus and Crimean-Congo Hemorrhagic Fever Virus (CCHFV), responsible for diseases with a high impact on public health (Wang and Crameri 2014; Belay et al. Hepatitis E virus (HEV) had been considered a sanitation problem in resource limited countries; however, the zoonotic form has emerged in industrialized countries with high seroprevalence, as detected in swine abattoir workers (Ukuli and Mugimba 2017) . The aim of this review is to identify observational studies that show evidence of association between human anti-HEV, anti-WNV and anti-CCHFV antibody seropositivity (IgG and/or IgM) and certain occupational groups at risk of exposure. Both zoonotic transmission pathways were also responsible for infections in farmers, agricultural workers and veterinarians enrolled in the epidemiological studies included in the review, with serologic IgG positivity ranging from 0.9% (Barzon et al.

abstract:
  Emerging viral infections represent a public health risk pointed out by the spreading of pathogens with potential zoonotic risk. Moreover, the risk of zoonosis has probably been underestimated in occupational settings. A literature review between 2007 and 2018 was performed to identify evidences concerning the epidemiological associations between some emerging viruses and occupational diseases. Observational studies and case-reports were selected and analyzed. West Nile Virus (WNV) disease, Crimean-Congo Hemorrhagic Fever (CCHF) disease and Hepatitis E virus (HEV) infection were included in the review for their potential zoonotic transmission. The most important risk factor for acquiring WNV infection and CCHF infection is the exposure to infected mosquitoes and ticks, respectively; therefore, outdoor workers are at risk of infection. HEV is responsible for epidemics and endemics of acute hepatitis in humans, that can become infected through waterborne, foodborne and zoonotic transmission routes. A total of 10, 34 and 45 eligible studies for WNV, CCHF virus (CCFHV) and HEV, respectively, were analyzed by year, country, study design, risk group and outcomes. The occupational risk groups mainly included farm and agricultural workers, veterinarians, slaughterers, animal handlers, healthcare workers and soldiers. These findings support the need to develop effective interventions to prevent transmission of emerging viruses.


id: cord-295455-km0qcmlh
title: Viral Macrodomains: Unique Mediators of Viral Replication and Pathogenesis
author: Fehr, Anthony R.
date: 2018-07-31
txt: ./txt/cord-295455-km0qcmlh.txt
cache: ./cache/cord-295455-km0qcmlh.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0966842X17302603
doi: 10.1016/j.tim.2017.11.011
summary:
  The recent discovery that mammalian macrodomain proteins enzymatically remove ADP-ribose, a common post-translation modification, from proteins has led to an outburst of studies describing both the enzymatic activity and function of viral macrodomains. These new studies have defined these domains as de-ADP-ribosylating enzymes, which indicates that these viruses have evolved to counteract antiviral ADP-ribosylation, likely mediated by poly-ADP-ribose polymerases (PARPs). Originally described as ADP-ribose-1 00 -phosphatases, both cellular and viral macrodomains enzymatically remove mono-and poly-ADP-ribose from proteins, supporting the notion that protein ADP-ribosylation is a component of the antiviral response. It was unclear how these mutations affected this protein, as neither mutant affected PAR binding and it was unknown whether alphaviruses'' macrodomains had de-ADP-ribosylating activity. Differential activities of cellular and viral macro domain proteins in binding of ADP-ribose metabolites The conserved macrodomains of the nonstructural proteins of Chikungunya virus and other pathogenic positive strand RNA viruses function as mono-ADP-ribosylhydrolases

abstract:
  Viruses from the Coronaviridae, Togaviridae, and Hepeviridae families ​all contain genes that encode a conserved protein domain, called a macrodomain; however, the role of this domain during infection has remained enigmatic. The recent discovery that mammalian macrodomain proteins enzymatically remove ADP-ribose, a common post-translation modification, from proteins has led to an outburst of studies describing both the enzymatic activity and function of viral macrodomains. These new studies have defined these domains as de-ADP-ribosylating enzymes, which indicates that these viruses have evolved to counteract antiviral ADP-ribosylation, likely mediated by poly-ADP-ribose polymerases (PARPs). Here, we comprehensively review this rapidly expanding field, describing the structures and enzymatic activities of viral macrodomains, and discussing their roles in viral replication and pathogenesis.


id: cord-297514-98q6kpmx
author: Salines, Morgane
date: 2018-01-01
txt: ./txt/cord-297514-98q6kpmx.txt
cache: ./cache/cord-297514-98q6kpmx.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/29290293/
doi: 10.1016/j.prevetmed.2017.11.015
summary:
  This study aimed to pair network analysis and epidemiological data in order to evaluate the impact of animal movements on pathogen prevalence in farms and assess the risk of local areas being exposed to diseases due to incoming movements. The aim of our study was therefore to combine network analysis with disease epidemiology and propose methods to quantify the epidemiological role of animal movements on two different scales: firstly by measuring the impact of animal movements on pathogen prevalence at the farm level; and secondly by assessing the risk of French départements 1 being exposed to diseases due to incoming movements from infected areas.

title:
  Combining network analysis with epidemiological data to inform risk-based surveillance: Application to hepatitis E virus (HEV) in pigs

abstract:
  Animal movements between farms are a major route of pathogen spread in the pig production sector. This study aimed to pair network analysis and epidemiological data in order to evaluate the impact of animal movements on pathogen prevalence in farms and assess the risk of local areas being exposed to diseases due to incoming movements. Our methodology was applied to hepatitis E virus (HEV), an emerging foodborne zoonotic agent of concern that is highly prevalent in pig farms. Firstly, the pig movement network in France (data recorded in 2013) and the results of a nation-wide seroprevalence study (data collected in 178 farms in 2009) were modelled and analysed. The link between network centrality measures of farms and HEV seroprevalence levels was explored using a generalised linear model. The in-degree and ingoing closeness of farms were found to be statistically associated with high HEV within-farm seroprevalence (p < 0.05). Secondly, the risk of a French département (i.e. French local administrative areas) being exposed to HEV was calculated by combining the distribution of farm-level HEV prevalence in source départements with the number of movements coming from those same départements. By doing so, the risk of exposure for départements was mapped, highlighting differences between geographical patterns of HEV prevalence and the risk of exposure to HEV. These results suggest that not only highly prevalent areas but also those having at-risk movements from infected areas should be monitored. Pathogen management and surveillance options in the pig production sector should therefore take animal movements into consideration, paving the way for the development of targeted and risk-based disease surveillance strategies.


id: cord-298233-qqhgmqrg
title: Molecular Biology and Infection of Hepatitis E Virus
author: Nan, Yuchen
date: 2016-09-07
url: https://doi.org/10.3389/fmicb.2016.01419
doi: 10.3389/fmicb.2016.01419
abstract:
  Hepatitis E virus (HEV) is a viral pathogen transmitted primarily via fecal-oral route. In humans, HEV mainly causes acute hepatitis and is responsible for large outbreaks of hepatitis across the world. The case fatality rate of HEV-induced hepatitis ranges from 0.5 to 3% in young adults and up to 30% in infected pregnant women. HEV strains infecting humans are classified into four genotypes. HEV strains from genotypes 3 and 4 are zoonotic, whereas those from genotypes 1 and 2 have no known animal reservoirs. Recently, notable progress has been accomplished for better understanding of HEV biology and infection, such as chronic HEV infection, in vitro cell culture system, quasi-enveloped HEV virions, functions of the HEV proteins, mechanism of HEV antagonizing host innate immunity, HEV pathogenesis and vaccine development. However, further investigation on the cross-species HEV infection, host tropism, vaccine efficacy, and HEV-specific antiviral strategy is still needed. This review mainly focuses on molecular biology and infection of HEV and offers perspective new insight of this enigmatic virus.


id: cord-298678-hjxph9jm
title: Viral Contamination of Food
author: Petrović, T.
date: 2016-02-05
txt: ./txt/cord-298678-hjxph9jm.txt
cache: ./cache/cord-298678-hjxph9jm.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/B978012800723500005X
doi: 10.1016/b978-0-12-800723-5.00005-x
summary:
  Results of surveys on the presence of viruses in different kind of foods commodities (fresh produces and shellfish) and in some cases connections to caused outbreaks are presented. Human Norovirus followed by hepatitis A virus are the most common foodborne viruses, which are transmitted by food consumed raw, such as shellfish, fresh vegetables, and berry fruit. These viruses have been identified in a variety of environmental samples, including wastewater, sludge, in marine, surface, and drinking waters, and shellfish, but no foodborne or waterborne outbreaks associated with the enteric HAdV have been reported (Greening, 2006) . The presented data suggest a high prevalence of different human enteric viruses, but mostly NoV, HAV, EV, HAdV, and HRV were found in shellfish samples collected from growing areas, as well as from the market in different countries.

abstract:
  A review of the relevant foodborne viruses is presented. Published data from scientific journals as well as the data presented in official reports and published on the Internet were used for this review. In the review, information is given for the main foodborne viruses, implicated virus species, and food matrices involved, some history data are given, as well as modes of transmission, and sources of the virus presence in food. Results of surveys on the presence of viruses in different kind of foods commodities (fresh produces and shellfish) and in some cases connections to caused outbreaks are presented. Also, possible zoonotic infection and implicated viruses that could be transmitted through food are given. Human Norovirus followed by hepatitis A virus are the most common foodborne viruses, which are transmitted by food consumed raw, such as shellfish, fresh vegetables, and berry fruit. In developed countries, hepatitis E virus is increasingly being recognized as an emerging viral foodborne pathogen that includes zoonotic transmission via pork products. The existing knowledge gaps and the major future expectations in the detection and surveillance of foodborne viruses are mentioned.


id: cord-316592-a1uhy2ex
title: RNA interference inhibits hepatitis E virus mRNA accumulation and protein synthesis in vitro
author: Huang, Fen
date: 2010-05-19
txt: ./txt/cord-316592-a1uhy2ex.txt
cache: ./cache/cord-316592-a1uhy2ex.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.vetmic.2009.10.023
doi: 10.1016/j.vetmic.2009.10.023
summary:
  To exploit the possibility of using RNA interference (RNAi) as a strategy against HEV infection, four small interference RNA (siRNA) duplex targeting ORF2 gene were constructed. Real-Time quantitative polymerase chain reaction (Real-Time qPCR) and Western blot assay demonstrated that four HEV specific siRNAs (si-ORF2-1, si-ORF2-2, si-ORF2-3 and si-ORF2-4) were capable of protecting cells against HEV infection with very high specificity and efficiency. Real-Time quantitative polymerase chain reaction (Real-Time qPCR) and Western blot assay demonstrated that four HEV specific siRNAs (si-ORF2-1, si-ORF2-2, si-ORF2-3 and si-ORF2-4) were capable of protecting cells against HEV infection with very high specificity and efficiency. The efficiency of suppression of the HEV ORF2 gene by various HEV specific siRNAs was evaluated by fluorescence microscopy, Real-Time qPCR and Western blot. RNA interference effectively inhibits mRNA accumulation and protein expression of hepatitis C virus core and E2 genes in human cells

abstract:
  Hepatitis E virus (HEV) is a zoonotic pathogen to which several species, including human beings, pigs and rodents, are reported to be susceptible. To date, vaccines developed against HEV still need to be improved and a structural gene (ORF2), which encodes a capsid protein with high sequence conservation found across HEV genotypes, is a potential candidate. To exploit the possibility of using RNA interference (RNAi) as a strategy against HEV infection, four small interference RNA (siRNA) duplex targeting ORF2 gene were constructed. A challenge against HEV infection by RNAi was performed in A549 cells. Real-Time quantitative polymerase chain reaction (Real-Time qPCR) and Western blot assay demonstrated that four HEV specific siRNAs (si-ORF2-1, si-ORF2-2, si-ORF2-3 and si-ORF2-4) were capable of protecting cells against HEV infection with very high specificity and efficiency. The results suggest that RNAi is a potent anti-HEV infection prophylaxis strategy.


id: cord-318222-o9kc3x6z
author: Saraswat, Shweta
date: 2020-01-23
txt: ./txt/cord-318222-o9kc3x6z.txt
cache: ./cache/cord-318222-o9kc3x6z.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32039053/
doi: 10.3389/fcimb.2019.00478
summary:
  title: Hepatitis E Virus Cysteine Protease Has Papain Like Properties Validated by in silico Modeling and Cell-Free Inhibition Assays The enzyme activity and the inhibition studies were conducted using Zymography, FTC-casein based protease assay and ORF1 polyprotein digestion. Hence, we propose that HEV-protease has characteristics of "Papain-like cysteine protease," as determined through structural homology, active site residues and class-specific inhibition. Four inhibitors (E64, Chymostatin, Leupeptin, and ALLN) showed good ligandreceptor interactions that correlated better with the enzyme inhibition activity of recombinant HEV PCP protein with Glide docking ( Table 2 ). On the basis of structural homology, active site residue and class specific inhibition we have classified HEV-protease as a "Papain-like cysteine protease." Molecular characterization of hepatitis E virus ORF1 gene supports a papain-like cysteine protease (PCP)-domain activity Molecular modeling and analysis of hepatitis E virus (HEV) papain-like cysteine protease

title:
  Hepatitis E Virus Cysteine Protease Has Papain Like Properties Validated by in silico Modeling and Cell-Free Inhibition Assays

abstract:
  Hepatitis E virus (HEV) has emerged as a global health concern during the last decade. In spite of a high mortality rate in pregnant women with fulminant hepatitis, no antiviral drugs or licensed vaccine is available in India. HEV-protease is a pivotal enzyme responsible for ORF1 polyprotein processing leading to cleavage of the non-structural enzymes involved in virus replication. HEV-protease region encoding 432–592 amino acids of Genotype-1 was amplified, expressed in Sf21 cells and purified in its native form. The recombinant enzyme was biochemically characterized using SDS-PAGE, Western blotting and Immunofluorescence. The enzyme activity and the inhibition studies were conducted using Zymography, FTC-casein based protease assay and ORF1 polyprotein digestion. To conduct ORF1 digestion assay, the polyprotein, natural substrate of HEV-protease, was expressed in E. coli and purified. Cleavage of 186 kDa ORF1 polyprotein by the recombinant HEV-protease lead to appearance of non-structural proteins viz. Methyltransferase, Protease, Helicase and RNA dependent RNA polymerase which were confirmed through immunoblotting using antibodies generated against specific epitopes of the enzymes. FTC-casein substrate was used for kinetic studies to determine Km and Vmax of the enzyme and also the effect of different metal ions and other protease inhibitors. A 95% inhibition was observed with E-64 which was validated through in silico analysis. The correlation coefficient between inhibition and docking score of Inhibitors was found to have a significant value of r(2) = 0.75. The predicted 3D model showed two domain architecture structures similar to Papain like cysteine protease though they differed in arrangements of alpha helices and beta sheets. Hence, we propose that HEV-protease has characteristics of “Papain-like cysteine protease,” as determined through structural homology, active site residues and class-specific inhibition. However, conclusive nature of the enzyme remains to be established.


id: cord-321132-xdpb3ukt
author: Lhomme, Sebastien
date: 2014-01-15
txt: ./txt/cord-321132-xdpb3ukt.txt
cache: ./cache/cord-321132-xdpb3ukt.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1093/infdis/jit438
doi: 10.1093/infdis/jit438
summary:
  We investigated the association between the genetic heterogeneity of HEV quasispecies in ORF1 and the outcome of infection in solid-organ transplant patients. Both sequence entropy and genetic distances during the hepatitis E acute phase were higher in patients whose infection became chronic than in those who cleared the virus. Both sequence entropy and genetic distances during the hepatitis E acute phase were higher in patients whose infection became chronic than in those who cleared the virus. We therefore analysed the characteristics of HEV quasispecies at the acute phase of hepatitis E in 2 groups of SOT patients, one whose infection became chronic and the other who cleared the virus. Both the complexity and diversity of the PPR and the macro domain were higher in viral population of the patients whose infection became chronic than in those who cleared the virus.

title:
  Influence of Polyproline Region and Macro Domain Genetic Heterogeneity on HEV Persistence in Immunocompromised Patients

abstract:
  Hepatitis E virus (HEV) can chronically infect immunocompromised patients. The polyproline region (PPR) and the macro domain of ORF1 protein may modulate virus production and/or the host immune response. We investigated the association between the genetic heterogeneity of HEV quasispecies in ORF1 and the outcome of infection in solid-organ transplant patients. Both sequence entropy and genetic distances during the hepatitis E acute phase were higher in patients whose infection became chronic than in those who cleared the virus. Hence, great quasispecies heterogeneity in the regions encoding the PPR and the macro domain may facilitate HEV persistence.


id: cord-322062-nnefbeo6
title: Hepatitis E virus (HEV): Molecular cloning and sequencing of the full-length viral genome
author: Tam, Albert W.
date: 1991-11-30
txt: ./txt/cord-322062-nnefbeo6.txt
cache: ./cache/cord-322062-nnefbeo6.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/1926770/
doi: 10.1016/0042-6822(91)90760-9
summary:
  We now report on the molecular cloning and sequencing of the complete HEV (Burma; B) viral genome together with the deduced amino acid sequences of viral-encoded proteins General perspectives on the genetic organization of the virus, as deduced from sequence and open reading frame analyses, indicate that HEV bears some similarity to the caliciviridae but may represent a new class of nonenveloped RNA virus. Bife was chosen as the RNA source for cDNA synthesis because it contained relatively large numbers of virus particles when HEV cDNA clones were identified from libraries made from randomly primed cyno bile (solid square), or from cyno liver after priming by oligo-dT (solid circle), random sequence hexamers (open circle) and HEV-sequence specific oligonucleotides (open square). The presence of HEV-specific subgenomic RNAs localized to the 3'' one-third of the genome suggests that these may be the transcripts from which these 3'' end ORFs are expressed and is indicative of a unique expression strategy among nonenveloped positive-sense RNA viruses infecting humans.

abstract:
  Abstract We have recently described the cloning of a portion of the hepatitis E virus (HEV) and confirmed its etiologic association with enterically transmitted (waterborne, epidemic) non-A, non-B hepatitis. The virus consists of a single-stranded, positive-sense RNA genome of approximately 7.5 kb, with a polyadenylated 3' end. We now report on the cloning and nucleotide sequencing of an overlapping, contiguous set of cDNA clones representing the entire genome of the HEV Burma strain [HEV(B)]. The largest open reading frame extends approximately 5 kb from the Fend and contains the RNA-directed RNA polymerase and nucleoside triphosphate binding motifs. The second major open reading frame (ORF2) begins 37 by downstream of the first and extends approximately 2 kb to the termination codon present 65 by from the 3' terminal stretch of poly(A) residues. ORF2 contains a consensus signal peptide sequence at its amino terminus and a capsid-like region with a high content of basic amino acids similar to that seen with other virus capsid proteins. A third open reading frame partially overlaps the first and second and encompasses only 369 bp. In addition to the 7.5-kb full-length genomic transcript, two subgenomic polyadenylated messages of approximately 3.7 and 2.0 kb were detected in infected liver using a probe from the 3' third of the genome. The genomic organization of the virus is consistent with the Fend encoding nonstructural and the 3' end encoding the viral structural gene(s). The expression strategy of the virus involves the use of three different open reading frames and at least three different transcripts. HEV was previously determined to be a nonenveloped particle with a diameter of 27–34 nm. These findings on the genetic organization and expression strategy of HEV suggest that it is the prototype human pathogen for a new class of RNA virus or perhaps a separate genus within the Caliciviridae family


id: cord-324216-ce3wa889
author: Wang, Zheng
date: 2008-12-01
txt: ./txt/cord-324216-ce3wa889.txt
cache: ./cache/cord-324216-ce3wa889.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/19046445/
doi: 10.1186/1471-2164-9-577
summary:
  Due to the great genetic diversity of HRV and HEV, in order to ensure that designed probes (referred to as probe sequences) generated from selected database sequences (referred to as prototype regions) would detect and discriminate all serotypes of HRV and HEV, a predictive model was used to assist the microarray design [17] . This study demonstrated the use of an algorithm for the design of probe sets based on an in silico predictive model [17] , developed by our group, that minimized the probes needed for detection and identification of most serotypes of HRV and HEV. A powerful feature of the expanded RPM-Flu v.30/31 resequencing pathogen microarray is that the nucleotide sequences generated from hybridization of the sample RNA/DNA and array-bound probe sets in conjunction with previously developed sequence analysis algorithm CIBSI can be easily interpreted to make serotype or strain identifications.

title:
  Resequencing microarray probe design for typing genetically diverse viruses: human rhinoviruses and enteroviruses

abstract:
  BACKGROUND: Febrile respiratory illness (FRI) has a high impact on public health and global economics and poses a difficult challenge for differential diagnosis. A particular issue is the detection of genetically diverse pathogens, i.e. human rhinoviruses (HRV) and enteroviruses (HEV) which are frequent causes of FRI. Resequencing Pathogen Microarray technology has demonstrated potential for differential diagnosis of several respiratory pathogens simultaneously, but a high confidence design method to select probes for genetically diverse viruses is lacking. RESULTS: Using HRV and HEV as test cases, we assess a general design strategy for detecting and serotyping genetically diverse viruses. A minimal number of probe sequences (26 for HRV and 13 for HEV), which were potentially capable of detecting all serotypes of HRV and HEV, were determined and implemented on the Resequencing Pathogen Microarray RPM-Flu v.30/31 (Tessarae RPM-Flu). The specificities of designed probes were validated using 34 HRV and 28 HEV strains. All strains were successfully detected and identified at least to species level. 33 HRV strains and 16 HEV strains could be further differentiated to serotype level. CONCLUSION: This study provides a fundamental evaluation of simultaneous detection and differential identification of genetically diverse RNA viruses with a minimal number of prototype sequences. The results demonstrated that the newly designed RPM-Flu v.30/31 can provide comprehensive and specific analysis of HRV and HEV samples which implicates that this design strategy will be applicable for other genetically diverse viruses.


id: cord-327609-no58ucyq
author: Murkey, Jamie A.
date: 2017-06-13
txt: ./txt/cord-327609-no58ucyq.txt
cache: ./cache/cord-327609-no58ucyq.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/28721353/
doi: 10.1093/ofid/ofx121
summary:
  We describe a case of genotype 3a HEV meningoencephalitis diagnosed by metagenomic next-generation sequencing, illustrating the power of an unbiased molecular approach to microbial testing and the first reported case of HEV infection presumably acquired through lung transplantation. We demonstrate the power of clinical mNGS in elucidating the cause of uncommon and unexpected infections and identify a case of chronic HEV infection most likely transmitted through the transplanted lungs the patient had received 6 years prior. The case patient is a 58-year-old woman with a history of idiopathic pulmonary fibrosis status post bilateral lung transplant in 2011, migraines, hypercoagulability, and multiple sclerosis (MS) on chronic immunosuppression who was admitted to University of California, Los Angeles Medical Center in October 2016 with 8 days of fever, headache, nausea, vomiting, neck stiffness, and photophobia. Treatment of HEV infection in patients with a solid-organ transplant and chronic hepatitis

title:
  Hepatitis E Virus–Associated Meningoencephalitis in a Lung Transplant Recipient Diagnosed by Clinical Metagenomic Sequencing

abstract:
  Hepatitis E virus (HEV) infection uncommonly causes chronic hepatitis and neurologic disease. We describe a case of genotype 3a HEV meningoencephalitis diagnosed by metagenomic next-generation sequencing, illustrating the power of an unbiased molecular approach to microbial testing and the first reported case of HEV infection presumably acquired through lung transplantation.


id: cord-329137-5pw07qje
author: Dryden, Kelly A.
date: 2012-10-05
txt: ./txt/cord-329137-5pw07qje.txt
cache: ./cache/cord-329137-5pw07qje.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/22743104/
doi: 10.1016/j.jmb.2012.06.029
summary:
  In addition, immature HAstV bears a striking resemblance to the structure of hepatitis E virus (HEV)-like particles, as previously predicted from structural similarity of the crystal structure of the astrovirus spike domain with the HEV P-domain [Dong, J., Dong, L., Méndez, E. Similarities between their capsid shells and dimeric spikes and between the sequences of their capsid proteins suggest that these viral families are phylogenetically related and may share common assembly and activation mechanisms. Immature, uncleaved particles, which are strikingly similar in appearance to HEV-like particles (HEV-lp), 14 Trypsin cleavage of the coat protein between the conserved (white boxes) and variable (shaded boxes) domains is required for viral maturation. If the cleaved proteins remain noncovalently associated with the capsid shell, then one would still expect to see surface density in the images of individual particles, even if the polypeptides do not conform to icosahedral symmetry.

title:
  Immature and Mature Human Astrovirus: Structure, Conformational Changes, and Similarities to Hepatitis E Virus

abstract:
  Abstract Human astroviruses (HAstVs) are a major cause of gastroenteritis. HAstV assembles from the structural protein VP90 and undergoes a cascade of proteolytic cleavages. Cleavage to VP70 is required for release of immature particles from cells, and subsequent cleavage by trypsin confers infectivity. We used electron cryomicroscopy and icosahedral image analysis to determine the first experimentally derived, three-dimensional structures of an immature VP70 virion and a fully proteolyzed, infectious virion. Both particles display T =3 icosahedral symmetry and nearly identical solid capsid shells with diameters of ~350Å. Globular spikes emanate from the capsid surface, yielding an overall diameter of ~440Å. While the immature particles display 90 dimeric spikes, the mature capsid only displays 30 spikes, located on the icosahedral 2-fold axes. Loss of the 60 peripentonal spikes likely plays an important role in viral infectivity. In addition, immature HAstV bears a striking resemblance to the structure of hepatitis E virus (HEV)-like particles, as previously predicted from structural similarity of the crystal structure of the astrovirus spike domain with the HEV P-domain [Dong, J., Dong, L., Méndez, E. & Tao, Y. (2011). Crystal structure of the human astrovirus capsid spike. Proc. Natl. Acad. Sci. USA 108, 12681–12686]. Similarities between their capsid shells and dimeric spikes and between the sequences of their capsid proteins suggest that these viral families are phylogenetically related and may share common assembly and activation mechanisms.


id: cord-332046-ihc031ly
author: Li, Yan‐Chao
date: 2013-01-01
txt: ./txt/cord-332046-ihc031ly.txt
cache: ./cache/cord-332046-ihc031ly.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1002/cne.23171
doi: 10.1002/cne.23171
summary:
  This study has systematically examined the assembly and dissemination of HEV 67N in the primary motor cortex of infected rats and provides additional evidence indicating that mem-branous-coating-mediated endo-/exocytosis can be used by HEV for its transsynaptic transfer. Consistent with the results in the previous experiments, the present study showed that at day 4 p.i. HEV-positive cells were observed in only a certain population of neurons with different sizes in layer V of the primary motor cortex (Fig. 1A,B) . Extracellular virions were not enclosed by any vesicular structures, whereas vesicle-enclosed virus particles were otherwise observed in the axonal terminals touching on the infected neurons, so it seemed that the virions within the synapses had acquired new vesicular membrane after entry. D shows a virion within a coated vesicle (arrow; see also the inset for details) in the axon terminal adjacent to an infected pyramidal cell.

title:
  Neurotropic virus tracing suggests a membranous‐coating‐mediated mechanism for transsynaptic communication

abstract:
  Swine hemagglutinating encephalomyelitis virus (HEV) has been shown to have a capability to propagate via neural circuits to the central nervous system after peripheral inoculation, resulting in acute deadly encephalomyelitis in natural host piglets as well as in experimental younger rodents. This study has systematically examined the assembly and dissemination of HEV 67N in the primary motor cortex of infected rats and provides additional evidence indicating that membranous‐coating‐mediated endo‐/exocytosis can be used by HEV for its transsynaptic transfer. In addition, our results suggested that this transsynaptic pathway could adapted for larger granular materials, such as viruses. These findings should help in understanding the mechanisms underlying coronavirus infections as well as the intercellular exchanges occurring at the synaptic junctions. J. Comp. Neurol. 521:203–212, 2013. © 2012 Wiley Periodicals, Inc.


id: cord-333966-st6gyozv
title: Design and production of a multiepitope construct derived from hepatitis E virus capsid protein
author: Taherkhani, Reza
date: 2015-03-17
txt: ./txt/cord-333966-st6gyozv.txt
cache: ./cache/cord-333966-st6gyozv.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1002/jmv.24171
doi: 10.1002/jmv.24171
summary:
  The aim of this study was to design a high density multiepitope protein, which can be a promising multiepitope vaccine candidate against Hepatitis E virus (HEV). Therefore, the present study was undertaken to design a high density multiepitope protein compromising four HTL epitopes with high-affinity binding to the HLA molecules using the in silico analysis, and to evaluate the immunological properties of this protein in vitro. In brief, approximately 1 Â 10 5 cells/well of PBMCs of each sample in RPMI 1640 and 10% FCS were added to four wells of round-bottom 96-well plates in total volume of 180 ml/well, stimulated with 20 ml/well of truncated ORF2 protein (10 mg/ml), high density multiepitope (10 mg/ml) and Phytohemagglutinin (PHA) (5 mg/ml) (Sigma-Aldrich) separately, and incubated at 37˚C for 4 days. IFN-g ELISPOT responses to high density multiepitope protein and truncated ORF2 protein were found significantly higher in HEV-recovered individuals than control group (P < 0.001).

abstract:
  The aim of this study was to design a high density multiepitope protein, which can be a promising multiepitope vaccine candidate against Hepatitis E virus (HEV). Initially, conserved and antigenic helper T‐lymphocyte (HTL) epitopes in the HEV capsid protein were predicted by in silico analysis. Subsequently, a multiepitope comprising four HTL epitopes with high‐affinity binding to the HLA molecules was designed, and repeated four times as high density multiepitope construct. This construct was synthesized and cloned into pET‐30a (+) vector. Then, it was transformed and expressed in Escherichia coli BL21 cells. The high density multiepitope protein was purified by Ni‐NTA agarose and concentrated using Amicon filters. Finally, the immunological properties of this high density multiepitope protein were evaluated in vitro. The results showed that the high density multiepitope construct was successfully expressed and purified. SDS‐PAGE and Western blot analyses showed the presence of a high density multiepitope protein band of approximately 33 kDa. Approximately 1 mg of the purified protein was obtained from each liter of the culture media. Moreover, the purified multiepitope protein was capable of induction of proliferation responses, IFN‐γ ELISPOT responses and IFN‐γ and IL‐12 cytokines production in a significant level in peripheral blood mononuclear cells (PBMCs) isolated from HEV‐recovered individuals compared to the control group. In conclusion, the newly produced multiepitope protein can induce significant T helper type 1 responses in vitro, and can be considered as a novel strategy for the development of HEV vaccines in the future. J. Med. Virol. 87:1225–1234, 2015. © 2015 Wiley Periodicals, Inc.


id: cord-335116-c83xyev5
author: Proença-Módena, José Luiz
date: 2014-07-21
txt: ./txt/cord-335116-c83xyev5.txt
cache: ./cache/cord-335116-c83xyev5.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/25128448/
doi: 10.1016/j.ijporl.2014.07.015
summary:
  Methods: The fluctuations of respiratory virus detection were compared to the major climatic variables during a two-year period using adenoids and palatine tonsils from 172 children with adenotonsillar hypertrophy and clinical evidence of obstructive sleep apnoea syndrome or recurrent adenotonsillitis, without symptoms of acute respiratory infection (ARI), by TaqMan real-time PCR. Methods: The fluctuations of respiratory virus detection were compared to the major climatic variables during a two-year period using adenoids and palatine tonsils from 172 children with adenotonsillar hypertrophy and clinical evidence of obstructive sleep apnoea syndrome or recurrent adenotonsillitis, without symptoms of acute respiratory infection (ARI), by TaqMan real-time PCR. We have previously reported high rates of detection of respiratory virus genomes in tonsils and adenoids from patients with chronic adenotonsillar diseases, suggesting a significant association of viruses, particularly picornaviruses, with severe tonsillar hypertrophy [3] .

title:
  Respiratory viruses are continuously detected in children with chronic tonsillitis throughout the year

abstract:
  OBJECTIVE: To evaluate the oscillations on the viral detection in adenotonsillar tissues from patients with chronic adenotonsillar diseases as an indicia of the presence of persistent viral infections or acute subclinical infections. STUDY DESIGN: Cross-sectional prospective study. SETTING: Tertiary hospital. METHODS: The fluctuations of respiratory virus detection were compared to the major climatic variables during a two-year period using adenoids and palatine tonsils from 172 children with adenotonsillar hypertrophy and clinical evidence of obstructive sleep apnoea syndrome or recurrent adenotonsillitis, without symptoms of acute respiratory infection (ARI), by TaqMan real-time PCR. RESULTS: The rate of detection of at least one respiratory virus in adenotonsillar tissue was 87%. The most frequently detected viruses were human adenovirus in 52.8%, human enterovirus in 47.2%, human rhinovirus in 33.8%, human bocavirus in 31.1%, human metapneumovirus in 18.3% and human respiratory syncytial virus in 17.2%. Although increased detection of human enterovirus occurred in summer/autumn months, and there were summer nadirs of human respiratory syncytial virus in both years of the study, there was no obvious viral seasonality in contrast to reports with ARI patients in many regions of the world. CONCLUSION: Respiratory viruses are continuously highly detected during whole year, and without any clinical symptomatology, indicating that viral genome of some virus can persist in lymphoepithelial tissues of the upper respiratory tract.


id: cord-336456-wg8vfh6w
author: Webb, Glynn W.
date: 2020-11-01
txt: ./txt/cord-336456-wg8vfh6w.txt
cache: ./cache/cord-336456-wg8vfh6w.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.clinmicnews.2020.10.001
doi: 10.1016/j.clinmicnews.2020.10.001
summary:
  However, HAV and HEV, which are isolated from the serum of individuals suffering an acute infection, are wrapped in a hijacked layer of host cell membrane, similar to those found on classical enveloped viruses but distinguished by the lack of any virusencoded proteins at the surface [8] . A recent large prospective study in Hong Kong identified both acute and chronic HEV-C1 infection in both immunocompetent and immunocompromised patients [24] . There is significant heterogeneity in the clinical picture of acute infection in these areas; only a small minority of patients present with typical viral hepatitis as described above. One of the most important public health challenges related to acute hepatitis E infection, which most commonly occurs in developing countries, is the excess morbidity and mortality seen among pregnant women (Table 1 ). Hepatitis E virus (HEV) infection in patients with cirrhosis is associated with rapid decompensation and death

title:
  Hepatitis A and Hepatitis E: Clinical and Epidemiological Features, Diagnosis, Treatment, and Prevention

abstract:
  Hepatitis A and E are both ancient diseases but have only been properly recognized as being caused by distinct pathogens in modern times. Despite significantly different genomic structures, both viruses employ remarkably similar strategies to avoid host detection and increase environmental transmission. There are millions of cases of acute viral hepatitis due to hepatitis A virus (HAV) and hepatitis E virus (HEV) each year, resulting in tens of thousands of deaths. The presentations can be clinically indistinguishable, but each virus also has a range of less common but more specific phenotypes. The epidemiology of HAV is complex, and is shifting in countries that are making improvements to public health and sanitation. HEV presents a significant public health challenge in resource-limited settings but has historically been incorrectly regarded as having little clinical relevance in industrialized countries.


id: cord-339382-ii4xurmr
title: Selected Viruses Detected on and in our Food
author: Bachofen, Claudia
date: 2018-03-21
txt: ./txt/cord-339382-ii4xurmr.txt
cache: ./cache/cord-339382-ii4xurmr.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1007/s40588-018-0087-9
doi: 10.1007/s40588-018-0087-9
summary:
  Two groups of viruses were selected: (a) the most important viruses contaminating food, based on numbers of publications in the last 5 years and (b) viruses infecting sources of food that might have an impact on human health. RECENT FINDINGS: Important foodborne viruses such as norovirus, hepatitis A and rotavirus are usually "only" contaminating food and are detected on the surface of foodstuffs. Furthermore, some plant viruses are known to infect and persist in insect-vectors and one of them, Tomato spotted wilt virus, a member of the genus Tospovirus of the Bunyaviridae family, was even shown to replicate in human cell lines [71] . HEV-3 and 4 strains infect humans, but the reservoir is thought to be in several animal species, whereof the pig plays the most important role for foodborne transmission. While foodborne HEV and TBEV clearly represent a threat for human public health, the role of several other viruses of animal origin detected in food still needs to be assessed.

abstract:
  PURPOSE OF REVIEW: The purpose of this review is to provide an update on recent literature and findings concerning selected foodborne viruses. Two groups of viruses were selected: (a) the most important viruses contaminating food, based on numbers of publications in the last 5 years and (b) viruses infecting sources of food that might have an impact on human health. RECENT FINDINGS: Important foodborne viruses such as norovirus, hepatitis A and rotavirus are usually “only” contaminating food and are detected on the surface of foodstuffs. However, they are threats to human public health and make up for the majority of cases. In contrast, the meaning of viruses born from within the food such as natural animal and plant viruses is still in many cases unknown. An exception is Hepatitis E virus that is endemic in pigs, transmitted via pork meat and is recognised as an emerging zoonosis in industrialised countries. SUMMARY: Even though the clinical meaning of “new” foodborne viruses, often detected by next generation sequencing, still needs clarification, the method has great potential to enhance surveillance and detection particularly in view of an increasingly globalised food trade.


id: cord-347244-abxv2mkz
title: Hepatitis E Virus Strains in Rabbits and Evidence of a Closely Related Strain in Humans, France
author: Izopet, Jacques
date: 2012-08-17
txt: ./txt/cord-347244-abxv2mkz.txt
cache: ./cache/cord-347244-abxv2mkz.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/22840216/
doi: 10.3201/eid1808.120057
summary:
  To determine HEV prevalence in rabbits and the strains'' genetic characteristics, we tested bile, liver, and additional samples from farmed and wild rabbits in France. Phylogenetic analysis based on a 1,400-nt fragment within ORF1, indicated that the ORF1 sequences from HEV strains from rabbits in France (n = 4) or China (n = 3) and the ORF1 sequence from the human strain TLS-18516human formed a distinct genetic group among sequences of HEV genotypes 1-4 (data not shown). We obtained the full-length genomic sequences of HEV strains from 2 wild rabbits in France and the TLS-18516-human strain. The phylogenetic tree, constructed by the neighbor-joining method using the full-length genomic sequences (including the sequences of genotypes 3f, 3e, and 3c, which were circulating in France), revealed that the HEV genomes from the rabbit strains and the TLS-18516-human strain belonged to the same clade.

abstract:
  Hepatitis E virus (HEV) strains from rabbits indicate that these mammals may be a reservoir for HEVs that cause infection in humans. To determine HEV prevalence in rabbits and the strains’ genetic characteristics, we tested bile, liver, and additional samples from farmed and wild rabbits in France. We detected HEV RNA in 7% (14/200) of bile samples from farmed rabbits (in 2009) and in 23% (47/205) of liver samples from wild rabbits (in 2007–2010). Full-length genomic sequences indicated that all rabbit strains belonged to the same clade (nucleotide sequences 72.2%–78.2% identical to HEV genotypes 1–4). Comparison with HEV sequences of human strains and reference sequences identified a human strain closely related to rabbit strain HEV. We found a 93-nt insertion in the X domain of open reading frame 1 of the human strain and all rabbit HEV strains. These findings indicate that the host range of HEV in Europe is expanding and that zoonotic transmission of HEV from rabbits is possible.


id: cord-348179-i8w7huke
title: Increased risk of hepatitis E virus infection in schizophrenia
author: Xue, Yong
date: 2012-10-07
txt: ./txt/cord-348179-i8w7huke.txt
cache: ./cache/cord-348179-i8w7huke.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1007/s00705-012-1494-5
doi: 10.1007/s00705-012-1494-5
summary:
  Moreover, schizophrenia patients with increased CD4(+)/CD8(+) T-cell ratios (>2.03) had higher anti-HEV IgG detection rates than those with normal ratios (1.05-2.03). Epidemiological studies have already shown that the rates of hepatitis B and hepatitis C virus infection in patients with schizophrenia were five and 11 times higher, respectively, than the estimated general population rates [26] . In the current study, we found that the detection rates for HEV antibodies in schizophrenia patients were much higher than those in healthy controls. In the present study, the detection rate of anti-HEV IgG in schizophrenia patients with increased CD4 ? T-cell levels and the increased risk of HEV infection in schizophrenia patients. Moreover, significant differences of the serum IL-4, IL-10 and IL-12 levels were observed among schizophrenia patients with and without HEV IgG antibodies. Taken together, schizophrenia patients exhibited higher risk of HEV infection than controls in the present study.

abstract:
  Until now, the risk of HEV infection in schizophrenia was unknown. The present results showed that the seroprevalence of anti-HEV IgG and anti-HEV IgM in schizophrenia were significantly higher than that in healthy controls. Anti-HEV IgG positivity increased with age and with the duration of disease in schizophrenia patients. Moreover, schizophrenia patients with increased CD4(+)/CD8(+) T-cell ratios (>2.03) had higher anti-HEV IgG detection rates than those with normal ratios (1.05-2.03). Compared with the schizophrenia patients who tested anti-HEV IgG negative, the levels of interleukin-4 and interleukin-10 (Th2 cytokines) were significantly higher, while the interleukin-12 (Th1 cytokine) level was significantly lower, in those with anti-HEV IgG positivity. Of five schizophrenia patients who were anti-HEV IgM positive, four had elevated CD4(+)/CD8(+) T-cell ratios. HEV RNA was isolated from one of these four patients and classified as genotype 4. Anti-HEV IgM positivity was not detected among healthy controls. Therefore, schizophrenia patients exhibited a higher risk of HEV infection than controls.


id: cord-350964-0jtfc271
author: Van Nguyen, Dung
date: 2018-02-28
txt: ./txt/cord-350964-0jtfc271.txt
cache: ./cache/cord-350964-0jtfc271.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3390/v10030102
doi: 10.3390/v10030102
summary:
  In this study of pegivirus and human hepatitis-related viruses, liver and serum samples from Vietnamese rodents and bats were examined by PCR and sequencing. Nucleic acids homologous to human hepatitis B, C, E viruses were detected in liver samples of 2 (1.3%) of 157 bats, 38 (8.1%), and 14 (3%) of 470 rodents, respectively. Hepacivirus-like viruses were frequently detected (42.7%) in the bamboo rat, Rhizomys pruinosus, while pegivirus RNA was only evident in 2 (0.3%) of 638 rodent serum samples. Nucleic acid that was extracted from liver samples of 157 bats (29 species; Table S1 ) and 470 rodents (six species) was screened for pegivirus and human hepatitis B, C, E viruses and their homologues ( Table 1 ) by nested and semi-nested PCR assays with degenerate primers.

title:
  Detection and Characterization of Homologues of Human Hepatitis Viruses and Pegiviruses in Rodents and Bats in Vietnam

abstract:
  Rodents and bats are now widely recognised as important sources of zoonotic virus infections in other mammals, including humans. Numerous surveys have expanded our knowledge of diverse viruses in a range of rodent and bat species, including their origins, evolution, and range of hosts. In this study of pegivirus and human hepatitis-related viruses, liver and serum samples from Vietnamese rodents and bats were examined by PCR and sequencing. Nucleic acids homologous to human hepatitis B, C, E viruses were detected in liver samples of 2 (1.3%) of 157 bats, 38 (8.1%), and 14 (3%) of 470 rodents, respectively. Hepacivirus-like viruses were frequently detected (42.7%) in the bamboo rat, Rhizomys pruinosus, while pegivirus RNA was only evident in 2 (0.3%) of 638 rodent serum samples. Complete or near-complete genome sequences of HBV, HEV and pegivirus homologues closely resembled those previously reported from rodents and bats. However, complete coding region sequences of the rodent hepacivirus-like viruses substantially diverged from all of the currently classified variants and potentially represent a new species in the Hepacivirus genus. Of the viruses identified, their routes of transmission and potential to establish zoonoses remain to be determined.


id: cord-351365-dc9t3vh3
author: Todt, Daniel
date: 2016-10-13
txt: ./txt/cord-351365-dc9t3vh3.txt
cache: ./cache/cord-351365-dc9t3vh3.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/27754363/
doi: 10.3390/v8100283
summary:
  Consequently, the onset of RBV treatment in chronically HEV-infected individuals can result in two divergent outcomes: viral extinction versus selection of fitness-enhanced viruses. Following an overview of RNA viruses treated with RBV in clinics and a summary of the different antiviral modes of action of this drug, we focus on the mutagenic effect of RBV on HEV intrahost populations, and how HEV is able to overcome lethal mutagenesis. Figure 1 provides an overview of a selection of RNA viruses against which RBV was shown to be active: hepatitis C virus (HCV, Flaviviridae), dengue virus (DENV, Flaviviridae), respiratory syncytial virus (RSV, Paramyxoviridae), influenza A and B virus (Orthomyxoviridae), chikungunya virus (CHIKV, Togaviridae), poliovirus (Picornaviridae), Hantaan virus (Bunyaviridae), and Lassa virus (Arenaviridae) [28, 29] ( Figure 1 ). Furthermore, mechanisms on the virus itself were described by inhibition of the capping efficiency, the viral polymerase, and a mutagenic effect on newly synthesized RNA genomes. A Mutation in the hepatitis E virus RNA polymerase promotes its replication and associates with ribavirin treatment failure in organ transplant recipients

title:
  Mutagenic Effects of Ribavirin on Hepatitis E Virus—Viral Extinction versus Selection of Fitness-Enhancing Mutations

abstract:
  Hepatitis E virus (HEV), an important agent of viral hepatitis worldwide, can cause severe courses of infection in pregnant women and immunosuppressed patients. To date, HEV infections can only be treated with ribavirin (RBV). Major drawbacks of this therapy are that RBV is not approved for administration to pregnant women and that the virus can acquire mutations, which render the intra-host population less sensitive or even resistant to RBV. One of the proposed modes of action of RBV is a direct mutagenic effect on viral genomes, inducing mismatches and subsequent nucleotide substitutions. These transition events can drive the already error-prone viral replication beyond an error threshold, causing viral population extinction. In contrast, the expanded heterogeneous viral population can facilitate selection of mutant viruses with enhanced replication fitness. Emergence of these mutant viruses can lead to therapeutic failure. Consequently, the onset of RBV treatment in chronically HEV-infected individuals can result in two divergent outcomes: viral extinction versus selection of fitness-enhanced viruses. Following an overview of RNA viruses treated with RBV in clinics and a summary of the different antiviral modes of action of this drug, we focus on the mutagenic effect of RBV on HEV intrahost populations, and how HEV is able to overcome lethal mutagenesis.


id: cord-351389-48tszqh5
author: Xu, Kai
date: 2013-10-10
txt: ./txt/cord-351389-48tszqh5.txt
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mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/24130486/
doi: 10.1371/journal.ppat.1003684
summary:
  title: Crystal Structure of the Hendra Virus Attachment G Glycoprotein Bound to a Potent Cross-Reactive Neutralizing Human Monoclonal Antibody One cross-reactive and receptor-blocking hmAb (m102.4) was recently demonstrated to be an effective post-exposure therapy in two animal models of NiV and HeV infection, has been used in several people on a compassionate use basis, and is currently in development for use in humans. We used X-ray crystallography to determine the high-resolution structures of the Hendra virus G glycoprotein in complex with a cross-reactive neutralizing human monoclonal antibody. Taken together, the success of hmAb m102.4 in vivo as an effective post-exposure treatment against henipavirus disease in two different well-characterized animal models (the ferret and nonhuman primate), along with the new detailed structural findings on its viral G glycoprotein binding features that help explain its superior cross-reactive neutralizing activity, will facilitate efforts aimed at obtaining approved human use application to treat accidental exposure to HeV or NiV infection.

title:
  Crystal Structure of the Hendra Virus Attachment G Glycoprotein Bound to a Potent Cross-Reactive Neutralizing Human Monoclonal Antibody

abstract:
  The henipaviruses, represented by Hendra (HeV) and Nipah (NiV) viruses are highly pathogenic zoonotic paramyxoviruses with uniquely broad host tropisms responsible for repeated outbreaks in Australia, Southeast Asia, India and Bangladesh. The high morbidity and mortality rates associated with infection and lack of licensed antiviral therapies make the henipaviruses a potential biological threat to humans and livestock. Henipavirus entry is initiated by the attachment of the G envelope glycoprotein to host cell membrane receptors. Previously, henipavirus-neutralizing human monoclonal antibodies (hmAb) have been isolated using the HeV-G glycoprotein and a human naïve antibody library. One cross-reactive and receptor-blocking hmAb (m102.4) was recently demonstrated to be an effective post-exposure therapy in two animal models of NiV and HeV infection, has been used in several people on a compassionate use basis, and is currently in development for use in humans. Here, we report the crystal structure of the complex of HeV-G with m102.3, an m102.4 derivative, and describe NiV and HeV escape mutants. This structure provides detailed insight into the mechanism of HeV and NiV neutralization by m102.4, and serves as a blueprint for further optimization of m102.4 as a therapeutic agent and for the development of entry inhibitors and vaccines.


