{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T03:16:05Z","timestamp":1793070965950,"version":"4.5.0"},"reference-count":117,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2016,9,1]],"date-time":"2016-09-01T00:00:00Z","timestamp":1472688000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2016,7,30]],"date-time":"2016-07-30T00:00:00Z","timestamp":1469836800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ebiomedicine.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["EBioMedicine"],"published-print":{"date-parts":[[2016,9]]},"DOI":"10.1016\/j.ebiom.2016.07.039","type":"journal-article","created":{"date-parts":[[2016,8,7]],"date-time":"2016-08-07T11:43:39Z","timestamp":1470570219000},"page":"31-42","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":74,"special_numbering":"C","title":["Hepatitis E Virus Mutations: Functional and Clinical Relevance"],"prefix":"10.1016","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7170-8810","authenticated-orcid":false,"given":"Hoang","family":"van Tong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nghiem Xuan","family":"Hoan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heiner","family":"Wedemeyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.-Thomas","family":"Bock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thirumalaisamy P.","family":"Velavan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"6","key":"10.1016\/j.ebiom.2016.07.039_bb0005","doi-asserted-by":"crossref","first-page":"2218","DOI":"10.1002\/hep.24674","article-title":"Hepatitis E","volume":"54","author":"Aggarwal","year":"2011","journal-title":"Hepatology"},{"issue":"1","key":"10.1016\/j.ebiom.2016.07.039_bb0010","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1006\/viro.2000.0819","article-title":"The 3\u2032 end of hepatitis E virus (HEV) genome binds specifically to the viral RNA-dependent RNA polymerase (RdRp)","volume":"282","author":"Agrawal","year":"2001","journal-title":"Virology"},{"issue":"19","key":"10.1016\/j.ebiom.2016.07.039_bb0015","doi-asserted-by":"crossref","first-page":"8803","DOI":"10.1128\/JVI.74.19.8803-8811.2000","article-title":"Helicase and capping enzyme active site mutations in brome mosaic virus protein 1a cause defects in template recruitment, negative-strand RNA synthesis, and viral RNA capping","volume":"74","author":"Ahola","year":"2000","journal-title":"J. Virol."},{"issue":"1","key":"10.1016\/j.ebiom.2016.07.039_bb0020","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1159\/000149370","article-title":"Evidence for a virus in non-A, non-B hepatitis transmitted via the fecal-oral route","volume":"20","author":"Balayan","year":"1983","journal-title":"Intervirology"},{"issue":"12","key":"10.1016\/j.ebiom.2016.07.039_bb0025","doi-asserted-by":"crossref","first-page":"3391","DOI":"10.1007\/s00705-014-2198-9","article-title":"Novel molecular alterations in the ORF 2 capsid gene of hepatitis E virus in patients with acute liver failure in North India","volume":"159","author":"Borkakoti","year":"2014","journal-title":"Arch. Virol."},{"key":"10.1016\/j.ebiom.2016.07.039_bb0030","article-title":"Report of a novel c1483w mutation in the hepatitis e virus polymerase in patients with acute liver failure","volume":"14","author":"Borkakoti","year":"2016","journal-title":"Infect. Genet. Evol."},{"issue":"6","key":"10.1016\/j.ebiom.2016.07.039_bb0035","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1016\/j.jhep.2010.08.037","article-title":"High viral load and deregulation of the progesterone receptor signaling pathway: association with hepatitis E-related poor pregnancy outcome","volume":"54","author":"Bose","year":"2011","journal-title":"J. Hepatol."},{"issue":"Pt 6","key":"10.1016\/j.ebiom.2016.07.039_bb0040","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1099\/vir.0.063602-0","article-title":"Evidence of extrahepatic replication of hepatitis E virus in human placenta","volume":"95","author":"Bose","year":"2014","journal-title":"J. Gen. Virol."},{"issue":"8","key":"10.1016\/j.ebiom.2016.07.039_bb0045","doi-asserted-by":"crossref","DOI":"10.1038\/emi.2012.7","article-title":"Molecular biology and replication of hepatitis E virus","volume":"1","author":"Cao","year":"2012","journal-title":"Emerg. Microbes Infect."},{"issue":"24","key":"10.1016\/j.ebiom.2016.07.039_bb0050","doi-asserted-by":"crossref","first-page":"13040","DOI":"10.1128\/JVI.01475-10","article-title":"The nucleotides on the stem-loop RNA structure in the junction region of the hepatitis E virus genome are critical for virus replication","volume":"84","author":"Cao","year":"2010","journal-title":"J. Virol."},{"issue":"14","key":"10.1016\/j.ebiom.2016.07.039_bb0055","doi-asserted-by":"crossref","first-page":"7100","DOI":"10.1128\/JVI.00403-08","article-title":"The hepatitis E virus ORF3 protein modulates epidermal growth factor receptor trafficking, STAT3 translocation, and the acute-phase response","volume":"82","author":"Chandra","year":"2008","journal-title":"J. Virol."},{"issue":"4","key":"10.1016\/j.ebiom.2016.07.039_bb0060","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1007\/s12038-008-0064-1","article-title":"Molecular biology and pathogenesis of hepatitis E virus","volume":"33","author":"Chandra","year":"2008","journal-title":"J. Biosci."},{"issue":"11","key":"10.1016\/j.ebiom.2016.07.039_bb0065","doi-asserted-by":"crossref","first-page":"5338","DOI":"10.1128\/JVI.02278-10","article-title":"Three amino acid mutations (F51L, T59A, and S390L) in the capsid protein of the hepatitis E virus collectively contribute to virus attenuation","volume":"85","author":"Cordoba","year":"2011","journal-title":"J. Virol."},{"issue":"9569","key":"10.1016\/j.ebiom.2016.07.039_bb0070","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1016\/S0140-6736(07)60595-9","article-title":"Locally acquired hepatitis E in chronic liver disease","volume":"369","author":"Dalton","year":"2007","journal-title":"Lancet"},{"issue":"10","key":"10.1016\/j.ebiom.2016.07.039_bb0075","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1056\/NEJMc0903778","article-title":"Persistent carriage of hepatitis E virus in patients with HIV infection","volume":"361","author":"Dalton","year":"2009","journal-title":"N. Engl. J. Med."},{"issue":"5","key":"10.1016\/j.ebiom.2016.07.039_bb0080","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1097\/01.qco.0000433308.83029.97","article-title":"Hepatitis E","volume":"26","author":"Dalton","year":"2013","journal-title":"Curr. Opin. Infect. Dis."},{"issue":"5","key":"10.1016\/j.ebiom.2016.07.039_bb0085","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1053\/j.gastro.2014.08.040","article-title":"A mutation in the hepatitis E virus RNA polymerase promotes its replication and associates with ribavirin treatment failure in organ transplant recipients","volume":"147","author":"Debing","year":"2014","journal-title":"Gastroenterology"},{"key":"10.1016\/j.ebiom.2016.07.039_bb0090","article-title":"Update on hepatitis E virology: implications for clinical practice","volume":"7","author":"Debing","year":"2016","journal-title":"J. Hepatol."},{"key":"10.1016\/j.ebiom.2016.07.039_bb0095","doi-asserted-by":"crossref","DOI":"10.1016\/j.jhep.2016.05.002","article-title":"Hepatitis E virus mutations associated with ribavirin treatment failure result in altered viral fitness and ribavirin sensitivity","author":"Debing","year":"2016","journal-title":"J. Hepatol."},{"key":"10.1016\/j.ebiom.2016.07.039_bb0100","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.virusres.2014.02.018","article-title":"Analysis of helicase domain mutations in the hepatitis E virus derived from patients with fulminant hepatic failure: effects on enzymatic activities and virus replication","volume":"184","author":"Devhare","year":"2014","journal-title":"Virus Res."},{"issue":"7","key":"10.1016\/j.ebiom.2016.07.039_bb0105","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1111\/jvh.12515","article-title":"Extra-hepatic replication and infection of hepatitis E virus in neuronal-derived cells","volume":"23","author":"Drave","year":"2016","journal-title":"J. Viral Hepat."},{"issue":"17","key":"10.1016\/j.ebiom.2016.07.039_bb0110","doi-asserted-by":"crossref","first-page":"8493","DOI":"10.1128\/JVI.00713-06","article-title":"Structural and functional basis for ADP-ribose and poly(ADP-ribose) binding by viral macro domains","volume":"80","author":"Egloff","year":"2006","journal-title":"J. Virol."},{"issue":"26","key":"10.1016\/j.ebiom.2016.07.039_bb0115","doi-asserted-by":"crossref","first-page":"15270","DOI":"10.1073\/pnas.251555098","article-title":"Recombinant hepatitis E virus genomes infectious for primates: importance of capping and discovery of a cis-reactive element","volume":"98","author":"Emerson","year":"2001","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.ebiom.2016.07.039_bb0120","doi-asserted-by":"crossref","first-page":"1468","DOI":"10.1099\/vir.0.051870-0","article-title":"An essential RNA element resides in a central region of hepatitis E virus ORF2","volume":"94(Pt 7)","author":"Emerson","year":"2013","journal-title":"J. Gen. Virol."},{"issue":"4","key":"10.1016\/j.ebiom.2016.07.039_bb0125","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1111\/liv.13085","article-title":"Causation by HEV of extrahepatic manifestations remains unproven","volume":"36","author":"Feng","year":"2016","journal-title":"Liver Int."},{"issue":"4","key":"10.1016\/j.ebiom.2016.07.039_bb0130","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1111\/tid.12411","article-title":"Relevance of chronic hepatitis E in liver transplant recipients: a real-life setting","volume":"17","author":"Galante","year":"2015","journal-title":"Transpl. Infect. Dis."},{"issue":"1","key":"10.1016\/j.ebiom.2016.07.039_bb0135","doi-asserted-by":"crossref","DOI":"10.5812\/hepatmon.15618","article-title":"Persistent hepatitis e virus genotype 4 infection in a child with acute lymphoblastic leukemia","volume":"14","author":"Geng","year":"2014","journal-title":"Hepat. Mon."},{"issue":"1","key":"10.1016\/j.ebiom.2016.07.039_bb0140","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.jhep.2015.08.034","article-title":"Detection and assessment of infectivity of hepatitis E virus in urine","volume":"64","author":"Geng","year":"2016","journal-title":"J. Hepatol."},{"key":"10.1016\/j.ebiom.2016.07.039_bb0145","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1111\/jvh.191_12425","article-title":"Antiviral therapy and viral fitness: temporal evolution of replication fitness HEV polymerase mutation during ribavirin therapy","volume":"22","author":"Gisa","year":"2015","journal-title":"J. Viral Hepat."},{"issue":"6","key":"10.1016\/j.ebiom.2016.07.039_bb0150","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/j.gastrohep.2011.02.011","article-title":"Chronic hepatitis E in an immunocompetent patient","volume":"34","author":"Gonzalez Tallon","year":"2011","journal-title":"Gastroenterol. Hepatol."},{"issue":"11","key":"10.1016\/j.ebiom.2016.07.039_bb0155","doi-asserted-by":"crossref","first-page":"6680","DOI":"10.1128\/JVI.79.11.6680-6689.2005","article-title":"The open reading frame 3 gene of hepatitis E virus contains a cis-reactive element and encodes a protein required for infection of macaques","volume":"79","author":"Graff","year":"2005","journal-title":"J. Virol."},{"issue":"2","key":"10.1016\/j.ebiom.2016.07.039_bb0160","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1128\/JVI.79.2.1017-1026.2005","article-title":"In vitro and in vivo mutational analysis of the 3\u2032-terminal regions of hepatitis e virus genomes and replicons","volume":"79","author":"Graff","year":"2005","journal-title":"J. Virol."},{"issue":"3","key":"10.1016\/j.ebiom.2016.07.039_bb0165","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1128\/JVI.01219-07","article-title":"Mutations within potential glycosylation sites in the capsid protein of hepatitis E virus prevent the formation of infectious virus particles","volume":"82","author":"Graff","year":"2008","journal-title":"J. Virol."},{"issue":"12","key":"10.1016\/j.ebiom.2016.07.039_bb0170","doi-asserted-by":"crossref","first-page":"2080","DOI":"10.1016\/j.ebiom.2015.11.020","article-title":"Hepatitis E virus superinfection and clinical progression in hepatitis B patients","volume":"2","author":"Hoan","year":"2015","journal-title":"EBioMedicine"},{"issue":"1","key":"10.1016\/j.ebiom.2016.07.039_bb0175","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1055\/s-0033-1338110","article-title":"Molecular virology of hepatitis E virus","volume":"33","author":"Holla","year":"2013","journal-title":"Semin. Liver Dis."},{"issue":"4","key":"10.1016\/j.ebiom.2016.07.039_bb0180","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1111\/tra.12260","article-title":"Hepatitis E virus enters liver cells through a dynamin-2, clathrin and membrane cholesterol-dependent pathway","volume":"16","author":"Holla","year":"2015","journal-title":"Traffic"},{"issue":"3","key":"10.1016\/j.ebiom.2016.07.039_bb0185","doi-asserted-by":"crossref","first-page":"1552","DOI":"10.1128\/JVI.79.3.1552-1558.2005","article-title":"Capped RNA transcripts of full-length cDNA clones of swine hepatitis E virus are replication competent when transfected into Huh7 cells and infectious when intrahepatically inoculated into pigs","volume":"79","author":"Huang","year":"2005","journal-title":"J. Virol."},{"issue":"6","key":"10.1016\/j.ebiom.2016.07.039_bb0190","doi-asserted-by":"crossref","first-page":"3018","DOI":"10.1128\/JVI.02259-06","article-title":"Initiation at the third in-frame AUG codon of open reading frame 3 of the hepatitis E virus is essential for viral infectivity in vivo","volume":"81","author":"Huang","year":"2007","journal-title":"J. Virol."},{"issue":"4","key":"10.1016\/j.ebiom.2016.07.039_bb0195","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1002\/jmv.20565","article-title":"Analysis of the full-length genome of genotype 4 hepatitis E virus isolates from patients with fulminant or acute self-limited hepatitis E","volume":"78","author":"Inoue","year":"2006","journal-title":"J. Med. Virol."},{"issue":"4","key":"10.1016\/j.ebiom.2016.07.039_bb0200","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1620\/tjem.218.279","article-title":"Nucleotide substitutions of hepatitis E virus genomes associated with fulminant hepatitis and disease severity","volume":"218","author":"Inoue","year":"2009","journal-title":"Tohoku J. Exp. Med."},{"issue":"1","key":"10.1016\/j.ebiom.2016.07.039_bb0205","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1128\/jvi.70.1.207-216.1996","article-title":"Expression in animal cells and characterization of the hepatitis E virus structural proteins","volume":"70","author":"Jameel","year":"1996","journal-title":"J. Virol."},{"issue":"9","key":"10.1016\/j.ebiom.2016.07.039_bb0210","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0025378","article-title":"Hepatitis E virus ORF2 protein activates the pro-apoptotic gene CHOP and anti-apoptotic heat shock proteins","volume":"6","author":"John","year":"2011","journal-title":"PLoS One"},{"issue":"6","key":"10.1016\/j.ebiom.2016.07.039_bb0215","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1111\/jvh.12157","article-title":"An ORF1-rearranged hepatitis E virus derived from a chronically infected patient efficiently replicates in cell culture","volume":"21","author":"Johne","year":"2014","journal-title":"J. Viral Hepat."},{"issue":"24","key":"10.1016\/j.ebiom.2016.07.039_bb0220","doi-asserted-by":"crossref","first-page":"12714","DOI":"10.1128\/JVI.00717-09","article-title":"Heparan sulfate proteoglycans are required for cellular binding of the hepatitis E virus ORF2 capsid protein and for viral infection","volume":"83","author":"Kalia","year":"2009","journal-title":"J. Virol."},{"issue":"8","key":"10.1016\/j.ebiom.2016.07.039_bb0225","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1056\/NEJMoa0706992","article-title":"Hepatitis E virus and chronic hepatitis in organ-transplant recipients","volume":"358","author":"Kamar","year":"2008","journal-title":"N. Engl. J. Med."},{"issue":"5","key":"10.1016\/j.ebiom.2016.07.039_bb0230","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1111\/j.1600-6143.2010.03068.x","article-title":"Hepatitis E virus-induced neurological symptoms in a kidney-transplant patient with chronic hepatitis","volume":"10","author":"Kamar","year":"2010","journal-title":"Am. J. Transplant."},{"issue":"9835","key":"10.1016\/j.ebiom.2016.07.039_bb0235","doi-asserted-by":"crossref","first-page":"2477","DOI":"10.1016\/S0140-6736(11)61849-7","article-title":"Hepatitis E","volume":"379","author":"Kamar","year":"2012","journal-title":"Lancet"},{"issue":"1","key":"10.1016\/j.ebiom.2016.07.039_bb0240","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1128\/CMR.00057-13","article-title":"Hepatitis E virus infection","volume":"27","author":"Kamar","year":"2014","journal-title":"Clin. Microbiol. Rev."},{"issue":"12","key":"10.1016\/j.ebiom.2016.07.039_bb0245","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1056\/NEJMoa1215246","article-title":"Ribavirin for chronic hepatitis E virus infection in transplant recipients","volume":"370","author":"Kamar","year":"2014","journal-title":"N. Engl. J. Med."},{"issue":"18","key":"10.1016\/j.ebiom.2016.07.039_bb0250","doi-asserted-by":"crossref","first-page":"9637","DOI":"10.1128\/JVI.00492-10","article-title":"RNA 5\u2032-triphosphatase activity of the hepatitis E virus helicase domain","volume":"84","author":"Karpe","year":"2010","journal-title":"J. Virol."},{"issue":"7","key":"10.1016\/j.ebiom.2016.07.039_bb0255","doi-asserted-by":"crossref","first-page":"3595","DOI":"10.1128\/JVI.02130-09","article-title":"NTPase and 5\u2032 to 3\u2032 RNA duplex-unwinding activities of the hepatitis E virus helicase domain","volume":"84","author":"Karpe","year":"2010","journal-title":"J. Virol."},{"issue":"7","key":"10.1016\/j.ebiom.2016.07.039_bb0260","doi-asserted-by":"crossref","first-page":"3793","DOI":"10.1128\/JVI.03582-14","article-title":"The lysine residues within the human ribosomal protein S17 sequence naturally inserted into the viral nonstructural protein of a unique strain of hepatitis E virus are important for enhanced virus replication","volume":"89","author":"Kenney","year":"2015","journal-title":"J. Virol."},{"issue":"17","key":"10.1016\/j.ebiom.2016.07.039_bb0265","doi-asserted-by":"crossref","first-page":"8259","DOI":"10.1073\/pnas.89.17.8259","article-title":"Computer-assisted assignment of functional domains in the nonstructural polyprotein of hepatitis E virus: delineation of an additional group of positive-strand RNA plant and animal viruses","volume":"89","author":"Koonin","year":"1992","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"issue":"1","key":"10.1016\/j.ebiom.2016.07.039_bb0270","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1128\/CMR.00062-13","article-title":"Host immune status and response to hepatitis E virus infection","volume":"27","author":"Krain","year":"2014","journal-title":"Clin. Microbiol. Rev."},{"issue":"3","key":"10.1016\/j.ebiom.2016.07.039_bb0275","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.ijgo.2003.11.018","article-title":"Hepatitis E in pregnancy","volume":"85","author":"Kumar","year":"2004","journal-title":"Int. J. Gynaecol. Obstet."},{"issue":"7","key":"10.1016\/j.ebiom.2016.07.039_bb0280","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1001005","article-title":"Quasispecies theory and the behavior of RNA viruses","volume":"6","author":"Lauring","year":"2010","journal-title":"PLoS Pathog."},{"issue":"2","key":"10.1016\/j.ebiom.2016.07.039_bb0285","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1053\/j.gastro.2015.10.048","article-title":"Chronic infection with camelid hepatitis E virus in a liver transplant recipient who regularly consumes camel meat and milk","volume":"150","author":"Lee","year":"2016","journal-title":"Gastroenterology"},{"issue":"1","key":"10.1016\/j.ebiom.2016.07.039_bb0290","doi-asserted-by":"crossref","first-page":"110","DOI":"10.3201\/eid1501.080296","article-title":"Hepatitis E virus genotype 3 diversity, France","volume":"15","author":"Legrand-Abravanel","year":"2009","journal-title":"Emerg. Infect. Dis."},{"issue":"2","key":"10.1016\/j.ebiom.2016.07.039_bb0295","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1093\/infdis\/jit438","article-title":"Influence of polyproline region and macro domain genetic heterogeneity on HEV persistence in immunocompromised patients","volume":"209","author":"Lhomme","year":"2014","journal-title":"J. Infect. Dis."},{"issue":"20","key":"10.1016\/j.ebiom.2016.07.039_bb0300","doi-asserted-by":"crossref","first-page":"12017","DOI":"10.1128\/JVI.01625-14","article-title":"Characterization of the polyproline region of the hepatitis E virus in immunocompromised patients","volume":"88","author":"Lhomme","year":"2014","journal-title":"J. Virol."},{"key":"10.1016\/j.ebiom.2016.07.039_bb0305","article-title":"Mutation in the hepatitis E virus polymerase and outcome of ribavirin therapy","author":"Lhomme","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"issue":"8","key":"10.1016\/j.ebiom.2016.07.039_bb0310","doi-asserted-by":"crossref","first-page":"2962","DOI":"10.3390\/ijms11082962","article-title":"A single amino acid substitution changes antigenicity of ORF2-encoded proteins of hepatitis E virus","volume":"11","author":"Liang","year":"2010","journal-title":"Int. J. Mol. Sci."},{"issue":"1","key":"10.1016\/j.ebiom.2016.07.039_bb0315","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.virusres.2008.06.005","article-title":"Mutational events during the primary propagation and consecutive passages of hepatitis E virus strain JE03-1760F in cell culture","volume":"137","author":"Lorenzo","year":"2008","journal-title":"Virus Res."},{"issue":"1","key":"10.1016\/j.ebiom.2016.07.039_bb0320","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1002\/rmv.482","article-title":"Phylogenetic analysis of global hepatitis E virus sequences: genetic diversity, subtypes and zoonosis","volume":"16","author":"Lu","year":"2006","journal-title":"Rev. Med. Virol."},{"issue":"4","key":"10.1016\/j.ebiom.2016.07.039_bb0325","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1002\/hep.28436","article-title":"A nationwide survey of hepatitis E viral infection in French blood donors","volume":"63","author":"Mansuy","year":"2016","journal-title":"Hepatology"},{"issue":"1","key":"10.1016\/j.ebiom.2016.07.039_bb0330","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.virusres.2011.01.016","article-title":"From barnyard to food table: the omnipresence of hepatitis E virus and risk for zoonotic infection and food safety","volume":"161","author":"Meng","year":"2011","journal-title":"Virus Res."},{"key":"10.1016\/j.ebiom.2016.07.039_bb0335","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.virusres.2013.11.022","article-title":"Mutagenesis of hepatitis E virus helicase motifs: effects on enzyme activity","volume":"179","author":"Mhaindarkar","year":"2014","journal-title":"Virus Res."},{"issue":"1","key":"10.1016\/j.ebiom.2016.07.039_bb0340","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/s11262-012-0833-7","article-title":"Hepatitis E virus from India exhibits significant amino acid mutations in fulminant hepatic failure patients","volume":"46","author":"Mishra","year":"2013","journal-title":"Virus Genes"},{"issue":"3","key":"10.1016\/j.ebiom.2016.07.039_bb0345","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1002\/jmv.20364","article-title":"Possible risk factors for the transmission of hepatitis E virus and for the severe form of hepatitis E acquired locally in Hokkaido, Japan","volume":"76","author":"Mizuo","year":"2005","journal-title":"J. Med. Virol."},{"issue":"29","key":"10.1016\/j.ebiom.2016.07.039_bb0350","doi-asserted-by":"crossref","first-page":"21124","DOI":"10.1074\/jbc.M701696200","article-title":"The hepatitis E virus Orf3 protein protects cells from mitochondrial depolarization and death","volume":"282","author":"Moin","year":"2007","journal-title":"J. Biol. Chem."},{"issue":"9","key":"10.1016\/j.ebiom.2016.07.039_bb0355","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1111\/j.1462-5822.2009.01340.x","article-title":"The hepatitis E virus ORF3 protein stabilizes HIF-1alpha and enhances HIF-1-mediated transcriptional activity through p300\/CBP","volume":"11","author":"Moin","year":"2009","journal-title":"Cell. Microbiol."},{"issue":"Pt 2","key":"10.1016\/j.ebiom.2016.07.039_bb0360","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1099\/vir.0.025791-0","article-title":"A PSAP motif in the ORF3 protein of hepatitis E virus is necessary for virion release from infected cells","volume":"92","author":"Nagashima","year":"2011","journal-title":"J. Gen. Virol."},{"issue":"Pt 12","key":"10.1016\/j.ebiom.2016.07.039_bb0365","doi-asserted-by":"crossref","first-page":"2838","DOI":"10.1099\/vir.0.035378-0","article-title":"Tumour susceptibility gene 101 and the vacuolar protein sorting pathway are required for the release of hepatitis E virions","volume":"92","author":"Nagashima","year":"2011","journal-title":"J. Gen. Virol."},{"issue":"4","key":"10.1016\/j.ebiom.2016.07.039_bb0370","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1005521","article-title":"Endoplasmic reticulum stress induced synthesis of a novel viral factor mediates efficient replication of genotype-1 hepatitis E virus","volume":"12","author":"Nair","year":"2016","journal-title":"PLoS Pathog."},{"issue":"9","key":"10.1016\/j.ebiom.2016.07.039_bb0375","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1111\/j.1478-3231.2008.01840.x","article-title":"Hepatitis E and pregnancy: understanding the pathogenesis","volume":"28","author":"Navaneethan","year":"2008","journal-title":"Liver Int."},{"key":"10.1016\/j.ebiom.2016.07.039_bb0380","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1099\/vir.0.037259-0","article-title":"A naturally occurring human\/hepatitis E recombinant virus predominates in serum but not in faeces of a chronic hepatitis E patient and has a growth advantage in cell culture","volume":"93(Pt 3)","author":"Nguyen","year":"2012","journal-title":"J. Gen. Virol."},{"issue":"2","key":"10.1016\/j.ebiom.2016.07.039_bb0385","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1016\/j.virusres.2013.07.020","article-title":"Molecular characterization of hepatitis E virus ORF1 gene supports a papain-like cysteine protease (PCP)-domain activity","volume":"178","author":"Parvez","year":"2013","journal-title":"Virus Res."},{"issue":"1","key":"10.1016\/j.ebiom.2016.07.039_bb0390","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.gene.2015.04.026","article-title":"The hepatitis E virus ORF1 \u2018X-domain\u2019 residues form a putative macrodomain protein\/Appr-1\u2033-pase catalytic-site, critical for viral RNA replication","volume":"566","author":"Parvez","year":"2015","journal-title":"Gene"},{"issue":"2","key":"10.1016\/j.ebiom.2016.07.039_bb0395","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.gene.2015.01.033","article-title":"The intergenic-junction variant (genotype 2 isolate) of hepatitis E virus restores the CREX \u2018stem-loop\u2019 structural integrity, essential for viral life cycle","volume":"559","author":"Parvez","year":"2015","journal-title":"Gene"},{"issue":"3","key":"10.1016\/j.ebiom.2016.07.039_bb0400","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1007\/s10616-014-9785-1","article-title":"Evidence of MAPK-JNK1\/2 activation by hepatitis E virus ORF3 protein in cultured hepatoma cells","volume":"67","author":"Parvez","year":"2015","journal-title":"Cytotechnology"},{"key":"10.1016\/j.ebiom.2016.07.039_bb0405","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.virusres.2013.11.016","article-title":"Molecular modeling and analysis of hepatitis E virus (HEV) papain-like cysteine protease","volume":"179","author":"Parvez","year":"2014","journal-title":"Virus Res."},{"issue":"4","key":"10.1016\/j.ebiom.2016.07.039_bb0410","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1159\/000431191","article-title":"Hepatitis E Virus","volume":"42","author":"Pauli","year":"2015","journal-title":"Transfus. Med. Hemother."},{"issue":"6","key":"10.1016\/j.ebiom.2016.07.039_bb0415","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1002\/rmv.1759","article-title":"V. Hepatitis E: current status","volume":"23","author":"Perez-Gracia","year":"2013","journal-title":"Rev. Med. Virol."},{"issue":"5","key":"10.1016\/j.ebiom.2016.07.039_bb0420","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1111\/j.1365-2893.2007.00858.x","article-title":"Fulminant liver failure from acute autochthonous hepatitis E in France: description of seven patients with acute hepatitis E and encephalopathy","volume":"14","author":"Peron","year":"2007","journal-title":"J. Viral Hepat."},{"issue":"3","key":"10.1016\/j.ebiom.2016.07.039_bb0425","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1111\/liv.12911","article-title":"Treatment of autochthonous acute hepatitis E with short-term ribavirin: a multicenter retrospective study","volume":"36","author":"Peron","year":"2016","journal-title":"Liver Int."},{"issue":"Pt 4","key":"10.1016\/j.ebiom.2016.07.039_bb0430","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1099\/vir.0.049577-0","article-title":"Early secretory pathway localization and lack of processing for hepatitis E virus replication protein pORF1","volume":"94","author":"Perttila","year":"2013","journal-title":"J. Gen. Virol."},{"issue":"35\u201336","key":"10.1016\/j.ebiom.2016.07.039_bb0435","first-page":"577","article-title":"Hepatitis E in Germany\u2014an under-reported infectious disease","volume":"111","author":"Pischke","year":"2014","journal-title":"Dtsch. Arztebl. Int."},{"issue":"1","key":"10.1016\/j.ebiom.2016.07.039_bb0440","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1128\/JVI.01854-08","article-title":"Deletions of the hypervariable region (HVR) in open reading frame 1 of hepatitis E virus do not abolish virus infectivity: evidence for attenuation of HVR deletion mutants in vivo","volume":"83","author":"Pudupakam","year":"2009","journal-title":"J. Virol."},{"issue":"19","key":"10.1016\/j.ebiom.2016.07.039_bb0445","doi-asserted-by":"crossref","first-page":"10031","DOI":"10.1128\/JVI.00763-11","article-title":"Mutational analysis of the hypervariable region of hepatitis e virus reveals its involvement in the efficiency of viral RNA replication","volume":"85","author":"Pudupakam","year":"2011","journal-title":"J. Virol."},{"issue":"4","key":"10.1016\/j.ebiom.2016.07.039_bb0450","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0035974","article-title":"The hepatitis E virus polyproline region is involved in viral adaptation","volume":"7","author":"Purdy","year":"2012","journal-title":"PLoS One"},{"issue":"7","key":"10.1016\/j.ebiom.2016.07.039_bb0455","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.3201\/eid2207.160168","article-title":"Hepatitis E virus infection in dromedaries, North and East Africa, United Arab Emirates, and Pakistan, 1983\u20132015","volume":"22","author":"Rasche","year":"2016","journal-title":"Emerg. Infect. Dis."},{"issue":"1","key":"10.1016\/j.ebiom.2016.07.039_bb0460","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/0042-6822(92)90716-3","article-title":"Indian hepatitis E virus shows a major deletion in the small open reading frame","volume":"189","author":"Ray","year":"1992","journal-title":"Virology"},{"issue":"1","key":"10.1016\/j.ebiom.2016.07.039_bb0465","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.virol.2007.07.036","article-title":"Subcellular localization of hepatitis E virus (HEV) replicase","volume":"370","author":"Rehman","year":"2008","journal-title":"Virology"},{"issue":"4948","key":"10.1016\/j.ebiom.2016.07.039_bb0470","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1126\/science.2107574","article-title":"Isolation of a cDNA from the virus responsible for enterically transmitted non-A, non-B hepatitis","volume":"247","author":"Reyes","year":"1990","journal-title":"Science"},{"issue":"6","key":"10.1016\/j.ebiom.2016.07.039_bb0475","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1016\/j.jinf.2014.10.016","article-title":"High hepatitis E virus seroprevalence with absence of chronic infection in HIV-infected patients","volume":"70","author":"Rivero-Juarez","year":"2015","journal-title":"J. Infect."},{"issue":"19","key":"10.1016\/j.ebiom.2016.07.039_bb0480","doi-asserted-by":"crossref","first-page":"9733","DOI":"10.1128\/JVI.00694-10","article-title":"Viral mutation rates","volume":"84","author":"Sanjuan","year":"2010","journal-title":"J. Virol."},{"issue":"6","key":"10.1016\/j.ebiom.2016.07.039_bb0485","doi-asserted-by":"crossref","first-page":"763","DOI":"10.2217\/fvl.15.29","article-title":"The emergence of hepatitis E virus in Europe","volume":"10","author":"Sayed","year":"2015","journal-title":"Futur. Virol."},{"issue":"10","key":"10.1016\/j.ebiom.2016.07.039_bb0490","doi-asserted-by":"crossref","first-page":"6031","DOI":"10.1128\/JVI.00444-13","article-title":"The hepatitis E virus capsid C-terminal region is essential for the viral life cycle: implication for viral genome encapsidation and particle stabilization","volume":"87","author":"Shiota","year":"2013","journal-title":"J. Virol."},{"issue":"6","key":"10.1016\/j.ebiom.2016.07.039_bb0495","doi-asserted-by":"crossref","first-page":"2438","DOI":"10.1073\/pnas.1018878108","article-title":"Cross-species infections of cultured cells by hepatitis E virus and discovery of an infectious virus-host recombinant","volume":"108","author":"Shukla","year":"2011","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"issue":"10","key":"10.1016\/j.ebiom.2016.07.039_bb0500","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1002\/ajh.20960","article-title":"Acute immune thrombocytopenia associated with hepatitis E in an adult","volume":"82","author":"Singh","year":"2007","journal-title":"Am. J. Hematol."},{"issue":"Pt 10","key":"10.1016\/j.ebiom.2016.07.039_bb0505","doi-asserted-by":"crossref","first-page":"2223","DOI":"10.1099\/vir.0.068429-0","article-title":"Consensus proposals for classification of the family Hepeviridae","volume":"95","author":"Smith","year":"2014","journal-title":"J. Gen. Virol."},{"issue":"3","key":"10.1016\/j.ebiom.2016.07.039_bb0510","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1099\/jgv.0.000393","article-title":"Proposed reference sequences for hepatitis E virus subtypes","volume":"97","author":"Smith","year":"2016","journal-title":"J. Gen. Virol."},{"issue":"3","key":"10.1016\/j.ebiom.2016.07.039_bb0515","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1002\/hep.24738","article-title":"Hepatitis E virus (HEV)-specific T-cell responses are associated with control of HEV infection","volume":"55","author":"Suneetha","year":"2012","journal-title":"Hepatology"},{"key":"10.1016\/j.ebiom.2016.07.039_bb0520","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/1471-2091-13-7","article-title":"The ORF2 glycoprotein of hepatitis E virus inhibits cellular NF-kappaB activity by blocking ubiquitination mediated proteasomal degradation of IkappaBalpha in human hepatoma cells","volume":"13","author":"Surjit","year":"2012","journal-title":"BMC Biochem."},{"issue":"4","key":"10.1016\/j.ebiom.2016.07.039_bb0525","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.hepres.2004.04.004","article-title":"Estimation of the mutation rate of hepatitis E virus based on a set of closely related 7.5-year-apart isolates from Sapporo, Japan","volume":"29","author":"Takahashi","year":"2004","journal-title":"Hepatol. Res."},{"issue":"5","key":"10.1016\/j.ebiom.2016.07.039_bb0530","doi-asserted-by":"crossref","first-page":"704","DOI":"10.3201\/eid1505.081100","article-title":"Virulent strain of hepatitis E virus genotype 3, Japan","volume":"15","author":"Takahashi","year":"2009","journal-title":"Emerg. Infect. Dis."},{"issue":"2","key":"10.1016\/j.ebiom.2016.07.039_bb0535","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1177\/0009922808327107","article-title":"Acute pancreatitis\u2014complicating hepatitis E virus infection in a 7-year-old boy with glucose 6 phosphate dehydrogenase deficiency","volume":"48","author":"Thapa","year":"2009","journal-title":"Clin. Pediatr. (Phila.)"},{"key":"10.1016\/j.ebiom.2016.07.039_bb0540","doi-asserted-by":"crossref","DOI":"10.1136\/gutjnl-2015-311000","article-title":"In vivo evidence for ribavirin-induced mutagenesis of the hepatitis E virus genome","author":"Todt","year":"2016","journal-title":"Gut"},{"issue":"25","key":"10.1016\/j.ebiom.2016.07.039_bb0545","doi-asserted-by":"crossref","first-page":"22759","DOI":"10.1074\/jbc.M200185200","article-title":"The phosphorylated form of the ORF3 protein of hepatitis E virus interacts with its non-glycosylated form of the major capsid protein, ORF2","volume":"277","author":"Tyagi","year":"2002","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ebiom.2016.07.039_bb0550","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1186\/1743-422X-7-129","article-title":"Recombination analysis reveals a double recombination event in hepatitis E virus","volume":"7","author":"Wang","year":"2010","journal-title":"Virol. J."},{"issue":"6","key":"10.1016\/j.ebiom.2016.07.039_bb0555","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.1053\/j.gastro.2012.02.014","article-title":"Pathogenesis and treatment of hepatitis e virus infection","volume":"142","author":"Wedemeyer","year":"2012","journal-title":"Gastroenterology"},{"issue":"38","key":"10.1016\/j.ebiom.2016.07.039_bb0560","doi-asserted-by":"crossref","first-page":"31618","DOI":"10.1074\/jbc.C112.401471","article-title":"A polymerase mechanism-based strategy for viral attenuation and vaccine development","volume":"287","author":"Weeks","year":"2012","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ebiom.2016.07.039_bb0565","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.meegid.2015.11.006","article-title":"Role of asparagine at position 562 in dimerization and immunogenicity of the hepatitis E virus capsid protein","volume":"37","author":"Xu","year":"2016","journal-title":"Infect. Genet. Evol."},{"issue":"6","key":"10.1016\/j.ebiom.2016.07.039_bb0570","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1038\/cmi.2008.56","article-title":"The Leu477 and Leu613 of ORF2-encoded protein are critical in forming neutralization antigenic epitope of hepatitis E virus genotype 4","volume":"5","author":"Zhang","year":"2008","journal-title":"Cell. Mol. Immunol."},{"issue":"10","key":"10.1016\/j.ebiom.2016.07.039_bb0575","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1056\/NEJMoa1406011","article-title":"Long-term efficacy of a hepatitis E vaccine","volume":"372","author":"Zhang","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.ebiom.2016.07.039_bb0580","doi-asserted-by":"crossref","first-page":"1728","DOI":"10.1099\/vir.0.019323-0","article-title":"Role of heat-shock protein 90 in hepatitis E virus capsid trafficking","volume":"91(Pt 7)","author":"Zheng","year":"2010","journal-title":"J. Gen. Virol."},{"issue":"24","key":"10.1016\/j.ebiom.2016.07.039_bb0585","doi-asserted-by":"crossref","first-page":"3157","DOI":"10.1016\/j.vaccine.2004.12.020","article-title":"A truncated ORF2 protein contains the most immunogenic site on ORF2: antibody responses to non-vaccine sequences following challenge of vaccinated and non-vaccinated macaques with hepatitis E virus","volume":"23","author":"Zhou","year":"2005","journal-title":"Vaccine"}],"container-title":["EBioMedicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2352396416303498?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2352396416303498?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2022,7,5]],"date-time":"2022-07-05T09:22:10Z","timestamp":1657012930000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2352396416303498"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,9]]},"references-count":117,"alternative-id":["S2352396416303498"],"URL":"https:\/\/doi.org\/10.1016\/j.ebiom.2016.07.039","relation":{},"ISSN":["2352-3964"],"issn-type":[{"value":"2352-3964","type":"print"}],"subject":[],"published":{"date-parts":[[2016,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Hepatitis E Virus Mutations: Functional and Clinical Relevance","name":"articletitle","label":"Article Title"},{"value":"EBioMedicine","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ebiom.2016.07.039","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2016 The Authors. Published by Elsevier B.V.","name":"copyright","label":"Copyright"}]}}