{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T00:13:47Z","timestamp":1793060027870,"version":"4.5.0"},"reference-count":100,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2020,7,28]],"date-time":"2020-07-28T00:00:00Z","timestamp":1595894400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Hepatitis E virus (HEV) is a leading cause of viral hepatitis in the world. It is usually responsible for acute hepatitis, but can lead to a chronic infection in immunocompromised patients. The host\u2019s innate immune response is the first line of defense against a virus infection; there is growing evidence that HEV RNA is recognized by toll-like receptors (TLRs) and retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs), leading to interferon (IFN) production. The IFNs activate interferon-stimulated genes (ISGs) to limit HEV replication and spread. HEV has developed strategies to counteract this antiviral response, by limiting IFN induction and signaling. This review summarizes the advances in our knowledge of intracellular pathogen recognition, interferon and inflammatory response, and the role of virus protein in immune evasion.<\/jats:p>","DOI":"10.3390\/vaccines8030422","type":"journal-article","created":{"date-parts":[[2020,7,28]],"date-time":"2020-07-28T10:16:49Z","timestamp":1595931409000},"page":"422","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Hepatitis E Virus: How It Escapes Host Innate Immunity"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7908-1576","authenticated-orcid":false,"given":"S\u00e9bastien","family":"Lhomme","sequence":"first","affiliation":[{"name":"National Reference Center for Hepatitis E Virus, Toulouse Purpan University Hospital, 31300 Toulouse, France"},{"name":"INSERM UMR1043, CNRS UMR5282, Center for Pathophysiology of Toulouse Purpan, 31300 Toulouse, France"},{"name":"Universit\u00e9 Toulouse III Paul Sabatier, 31330 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7791-3201","authenticated-orcid":false,"given":"Marion","family":"Migueres","sequence":"additional","affiliation":[{"name":"National Reference Center for Hepatitis E Virus, Toulouse Purpan University Hospital, 31300 Toulouse, France"},{"name":"INSERM UMR1043, CNRS UMR5282, Center for Pathophysiology of Toulouse Purpan, 31300 Toulouse, France"},{"name":"Universit\u00e9 Toulouse III Paul Sabatier, 31330 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Abravanel","sequence":"additional","affiliation":[{"name":"National Reference Center for Hepatitis E Virus, Toulouse Purpan University Hospital, 31300 Toulouse, France"},{"name":"INSERM UMR1043, CNRS UMR5282, Center for Pathophysiology of Toulouse Purpan, 31300 Toulouse, France"},{"name":"Universit\u00e9 Toulouse III Paul Sabatier, 31330 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9702-1833","authenticated-orcid":false,"given":"Olivier","family":"Marion","sequence":"additional","affiliation":[{"name":"INSERM UMR1043, CNRS UMR5282, Center for Pathophysiology of Toulouse Purpan, 31300 Toulouse, France"},{"name":"Universit\u00e9 Toulouse III Paul Sabatier, 31330 Toulouse, France"},{"name":"Department of Nephrology and Organs Transplantation, Toulouse Rangueil University Hospital, 31400 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1930-8964","authenticated-orcid":false,"given":"Nassim","family":"Kamar","sequence":"additional","affiliation":[{"name":"INSERM UMR1043, CNRS UMR5282, Center for Pathophysiology of Toulouse Purpan, 31300 Toulouse, France"},{"name":"Universit\u00e9 Toulouse III Paul Sabatier, 31330 Toulouse, France"},{"name":"Department of Nephrology and Organs Transplantation, Toulouse Rangueil University Hospital, 31400 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8462-3234","authenticated-orcid":false,"given":"Jacques","family":"Izopet","sequence":"additional","affiliation":[{"name":"National Reference Center for Hepatitis E Virus, Toulouse Purpan University Hospital, 31300 Toulouse, France"},{"name":"INSERM UMR1043, CNRS UMR5282, Center for Pathophysiology of Toulouse Purpan, 31300 Toulouse, France"},{"name":"Universit\u00e9 Toulouse III Paul Sabatier, 31330 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,28]]},"reference":[{"key":"ref_1","unstructured":"European Association for the Study of the Liver (2018). EASL Clinical Practice Guidelines on hepatitis E virus infection. J. Hepatol."},{"key":"ref_2","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":"ref_3","doi-asserted-by":"crossref","first-page":"17086","DOI":"10.1038\/nrdp.2017.86","article-title":"Hepatitis E virus infection","volume":"3","author":"Kamar","year":"2017","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1038\/nrneurol.2015.234","article-title":"Hepatitis E virus and neurological injury","volume":"12","author":"Dalton","year":"2016","journal-title":"Nat. Rev. Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1111\/liv.13037","article-title":"Extrahepatic manifestations of hepatitis E virus","volume":"36","author":"Kamar","year":"2016","journal-title":"Liver Int."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1935","DOI":"10.1111\/ajt.12253","article-title":"How should hepatitis E virus infection be defined in organ-transplant recipients?","volume":"13","author":"Kamar","year":"2013","journal-title":"Am. J. Transplant."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Smith, D.B., and Simmonds, P. (2018). Classification and genomic diversity of enterically transmitted hepatitis viruses. Cold Spring Harb. Perspect. Med., 8.","DOI":"10.1101\/cshperspect.a031880"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Smith, D.B., Izopet, J., Nicot, F., Simmonds, P., Jameel, S., Meng, X.J., Norder, H., Okamoto, H., van der Poel, W.H.M., and Reuter, G. (2020). Update: Proposed reference sequences for subtypes of hepatitis E virus (species Orthohepevirus A). J. Gen. Virol.","DOI":"10.1099\/jgv.0.001435"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2241","DOI":"10.3201\/eid2412.180937","article-title":"Rat hepatitis E virus as cause of persistent hepatitis after liver transplant","volume":"24","author":"Sridhar","year":"2018","journal-title":"Emerg. Infect. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Sridhar, S., Yip, C.C., Wu, S., Chew, N.F., Leung, K.H., Chan, J.F., Zhao, P.S., Chan, W.M., Poon, R.W., and Tsoi, H.W. (2020). Transmission of rat hepatitis E virus infection to humans in Hong Kong: A clinical and epidemiological analysis. Hepatology.","DOI":"10.1002\/hep.31138"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Andonov, A., Robbins, M., Borlang, J., Cao, J., Hattchete, T., Stueck, A., Deschaumbault, Y., Murnaghan, K., Varga, J., and Johnston, B. (2019). Rat hepatitis E virus linked to severe acute hepatitis in an immunocompetent patient. J. Infect. Dis.","DOI":"10.1093\/infdis\/jiz025"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Wang, B., Harms, D., Yang, X.L., and Bock, C.T. (2020). Orthohepevirus C: An expanding species of emerging hepatitis E virus variants. Pathogens, 9.","DOI":"10.3390\/pathogens9030154"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Kenney, S.P., and Meng, X.J. (2019). Hepatitis E virus genome structure and replication strategy. Cold Spring Harb. Perspect. Med., 9.","DOI":"10.1101\/cshperspect.a031724"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"LeDesma, R., Nimgaonkar, I., and Ploss, A. (2019). Hepatitis E virus replication. Viruses, 11.","DOI":"10.3390\/v11080719"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Proudfoot, A., Hyrina, A., Holdorf, M., Frank, A.O., and Bussiere, D. (2019). First crystal structure of a nonstructural hepatitis E viral protein identifies a putative novel zinc-binding protein. J. Virol., 93.","DOI":"10.1128\/JVI.00170-19"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/s13062-015-0050-0","article-title":"Sequence analysis reveals a conserved extension in the capping enzyme of the alphavirus supergroup, and a homologous domain in nodaviruses","volume":"10","author":"Ahola","year":"2015","journal-title":"Biol. Direct"},{"key":"ref_17","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. USA"},{"key":"ref_18","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","author":"Nguyen","year":"2012","journal-title":"J. Gen. Virol."},{"key":"ref_19","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":"ref_20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fmicb.2020.00001","article-title":"Insertions and duplications in the polyproline region of the hepatitis E Virus","volume":"11","author":"Lhomme","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref_21","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."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4773","DOI":"10.1073\/pnas.1721345115","article-title":"Origin, antigenicity, and function of a secreted form of ORF2 in hepatitis E virus infection","volume":"115","author":"Yin","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1073\/pnas.1614955114","article-title":"Hepatitis E virus ORF3 is a functional ion channel required for release of infectious particles","volume":"114","author":"Ding","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Gouttenoire, J., Pollan, A., Abrami, L., Oechslin, N., Mauron, J., Matter, M., Oppliger, J., Szkolnicka, D., Dao Thi, V.L., and van der Goot, F.G. (2018). Palmitoylation mediates membrane association of hepatitis E virus ORF3 protein and is required for infectious particle secretion. PLoS Pathog., 14.","DOI":"10.1371\/journal.ppat.1007471"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Nair, V.P., Anang, S., Subramani, C., Madhvi, A., Bakshi, K., Srivastava, A., Ranjith Kumar, C.T., and Surjit, M. (2016). Endoplasmic reticulum stress induced synthesis of a novel viral factor mediates efficient replication of genotype-1 hepatitis E virus. PLoS Pathog., 12.","DOI":"10.1371\/journal.ppat.1005521"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.tim.2013.10.005","article-title":"Peek-a-boo: Membrane hijacking and the pathogenesis of viral hepatitis","volume":"22","author":"Feng","year":"2014","journal-title":"Trends Microbiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1146\/annurev-virology-031413-085359","article-title":"Naked viruses that aren\u2019t always naked: Quasi-enveloped agents of acute hepatitis","volume":"1","author":"Feng","year":"2014","journal-title":"Annu Rev. Virol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1099\/vir.0.82535-0","article-title":"Development and evaluation of an efficient cell-culture system for Hepatitis E virus","volume":"88","author":"Tanaka","year":"2007","journal-title":"J. Gen. Virol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1906","DOI":"10.1128\/JCM.00629-09","article-title":"Development and characterization of a genotype 4 hepatitis E virus cell culture system using a HE-JF5\/15F strain recovered from a fulminant hepatitis patient","volume":"47","author":"Tanaka","year":"2009","journal-title":"J. Clin. Microbiol."},{"key":"ref_30","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. USA"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"5697","DOI":"10.1128\/JVI.00146-12","article-title":"Adaptation of a genotype 3 hepatitis E virus to efficient growth in cell culture depends on an inserted human gene segment acquired by recombination","volume":"86","author":"Shukla","year":"2012","journal-title":"J. Virol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1128\/JVI.02205-13","article-title":"Hepatitis E virus genotype 1 infection of swine kidney cells in vitro is inhibited at multiple levels","volume":"88","author":"Nguyen","year":"2014","journal-title":"J. Virol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4838","DOI":"10.1128\/JVI.78.9.4838-4846.2004","article-title":"In vitro replication of hepatitis E virus (HEV) genomes and of an HEV replicon expressing green fluorescent protein","volume":"78","author":"Emerson","year":"2004","journal-title":"J. Virol."},{"key":"ref_34","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."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.antiviral.2019.01.007","article-title":"Cell culture systems for the study of hepatitis E virus","volume":"163","author":"Meister","year":"2019","journal-title":"Antiviral Res."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Fu, R.M., Decker, C.C., and Dao Thi, V.L. (2019). Cell culture models for hepatitis E Virus. Viruses, 11.","DOI":"10.3390\/v11070608"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1677","DOI":"10.1038\/s41467-020-15337-2","article-title":"Stem cell-derived polarized hepatocytes","volume":"11","author":"Wu","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Capelli, N., Marion, O., Dubois, M., Allart, S., Bertrand-Michel, J., Lhomme, S., Abravanel, F., Izopet, J., and Chapuy-Regaud, S. (2019). Vectorial release of hepatitis E virus in polarized human hepatocytes. J. Virol., 93.","DOI":"10.1128\/JVI.01207-18"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"197765","DOI":"10.1016\/j.virusres.2019.197765","article-title":"In vivo models for studying Hepatitis E virus infection; Updates and applications","volume":"274","author":"Sayed","year":"2019","journal-title":"Virus Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1146\/annurev-animal-020518-115117","article-title":"Hepatitis E virus: Animal models and zoonosis","volume":"7","author":"Kenney","year":"2019","journal-title":"Annu Rev. Anim. Biosci."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Li, Y., Qu, C., Yu, P., Ou, X., Pan, Q., and Wang, W. (2019). The interplay between host innate immunity and hepatitis E virus. Viruses, 11.","DOI":"10.3390\/v11060541"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1038\/s41564-019-0421-x","article-title":"Decoding type I and III interferon signalling during viral infection","volume":"4","author":"Mesev","year":"2019","journal-title":"Nat. Microbiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1101\/SQB.1989.054.01.003","article-title":"Approaching the asymptote? Evolution and revolution in immunology","volume":"54","author":"Janeway","year":"1989","journal-title":"Cold Spring Harb. Symp. Quant. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/j.cell.2010.01.022","article-title":"Pattern recognition receptors and inflammation","volume":"140","author":"Takeuchi","year":"2010","journal-title":"Cell"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"16739","DOI":"10.1074\/jbc.M414139200","article-title":"Distinct poly(I-C) and virus-activated signaling pathways leading to interferon-beta production in hepatocytes","volume":"280","author":"Li","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/j.tim.2017.01.001","article-title":"Transcriptional regulation of antiviral interferon-stimulated genes","volume":"25","author":"Wang","year":"2017","journal-title":"Trends Microbiol."},{"key":"ref_47","first-page":"219","article-title":"Innate immune responses to hepatitis C virus","volume":"369","author":"Schoggins","year":"2013","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"26827","DOI":"10.1038\/srep26827","article-title":"Innate immune responses in human hepatocyte-derived cell lines alter genotype 1 hepatitis E virus replication efficiencies","volume":"6","author":"Devhare","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Devhare, P.B., Chatterjee, S.N., Arankalle, V.A., and Lole, K.S. (2013). Analysis of antiviral response in human epithelial cells infected with hepatitis E virus. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0063793"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Choi, Y.H., Zhang, X., Tran, C., and Skinner, B. (2018). Expression profiles of host immune response-related genes against HEV genotype 3 and genotype 1 infections in rhesus macaques. J. Viral Hepat.","DOI":"10.1111\/jvh.12890"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"a016246","DOI":"10.1101\/cshperspect.a016246","article-title":"Microbial sensing by Toll-like receptors and intracellular nucleic acid sensors","volume":"7","author":"Pandey","year":"2014","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Jagya, N., Varma, S.P., Thakral, D., Joshi, P., Durgapal, H., and Panda, S.K. (2014). RNA-seq based transcriptome analysis of hepatitis E virus (HEV) and hepatitis B virus (HBV) replicon transfected Huh-7 cells. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0087835"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1002\/hep.29105","article-title":"RIG-I is a key antiviral interferon-stimulated gene against hepatitis E virus regardless of interferon production","volume":"65","author":"Xu","year":"2017","journal-title":"Hepatology"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"104743","DOI":"10.1016\/j.antiviral.2020.104743","article-title":"MDA5 against enteric viruses through induction of interferon-like response partially via the JAK-STAT cascade","volume":"176","author":"Li","year":"2020","journal-title":"Antiviral Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3352","DOI":"10.1096\/fj.201600356R","article-title":"IFN regulatory factor 1 restricts hepatitis E virus replication by activating STAT1 to induce antiviral IFN-stimulated genes","volume":"30","author":"Xu","year":"2016","journal-title":"FASEB J."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Yin, X., Li, X., Ambardekar, C., Hu, Z., Lhomme, S., and Feng, Z. (2017). Hepatitis E virus persists in the presence of a type III interferon response. PLoS Pathog., 13.","DOI":"10.1371\/journal.ppat.1006417"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2096","DOI":"10.1002\/hep.29702","article-title":"The RNA genome of hepatitis E virus robustly triggers an antiviral interferon response","volume":"67","author":"Wang","year":"2018","journal-title":"Hepatology"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1073\/pnas.1912307117","article-title":"Robust hepatitis E virus infection and transcriptional response in human hepatocytes","volume":"117","author":"Todt","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1093\/infdis\/jiy603","article-title":"Analysis of IgG anti-HEV antibody protective levels during hepatitis E virus reinfection in experimentally infected rhesus macaques","volume":"219","author":"Choi","year":"2019","journal-title":"J. Infect. Dis."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1038\/ni.1782","article-title":"Activation of innate immune antiviral responses by Nod2","volume":"10","author":"Sabbah","year":"2009","journal-title":"Nat. Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1038\/nrmicro.2016.45","article-title":"Viral evasion of intracellular DNA and RNA sensing","volume":"14","author":"Chan","year":"2016","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Sooryanarain, H., Heffron, C.L., and Meng, X.J. (2020). The U-rich untranslated region of the hepatitis E virus induces differential type I and type III interferon responses in a host cell-dependent manner. mBio, 11.","DOI":"10.1128\/mBio.03103-19"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"9059","DOI":"10.1128\/JVI.00593-10","article-title":"Release of genotype 1 hepatitis E virus from cultured hepatoma and polarized intestinal cells depends on open reading frame 3 protein and requires an intact PXXP motif","volume":"84","author":"Emerson","year":"2010","journal-title":"J. Virol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1053\/j.gastro.2017.10.041","article-title":"Pan-genotype hepatitis E virus replication in stem cell-derived hepatocellular systems","volume":"154","author":"Wu","year":"2018","journal-title":"Gastroenterology"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"11264","DOI":"10.1128\/JVI.01205-10","article-title":"Pathogenesis of hepatitis E virus and hepatitis C virus in chimpanzees: Similarities and differences","volume":"84","author":"Yu","year":"2010","journal-title":"J. Virol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"154816","DOI":"10.1016\/j.cyto.2019.154816","article-title":"IFN-lambda3 as a host immune response in acute hepatitis E virus infection","volume":"125","author":"Murata","year":"2020","journal-title":"Cytokine"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Marion, O., Lhomme, S., Nayrac, M., Dubois, M., Pucelle, M., Requena, M., Migueres, M., Abravanel, F., Peron, J.M., and Carrere, N. (2019). Hepatitis E virus replication in human intestinal cells. Gut.","DOI":"10.1136\/gutjnl-2019-319004"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1544","DOI":"10.1111\/j.1572-0241.2002.05740.x","article-title":"Severe hemolysis and renal failure in glucose-6-phosphate dehydrogenase deficient patients with hepatitis E","volume":"97","author":"Abid","year":"2002","journal-title":"Am. J. Gastroenterol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"4748","DOI":"10.1038\/s41467-018-07200-2","article-title":"Genotype specific pathogenicity of hepatitis E virus at the human maternal-fetal interface","volume":"9","author":"Gouilly","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1002\/hep4.1138","article-title":"Hepatitis E Virus replication and interferon responses in human placental cells","volume":"2","author":"Knegendorf","year":"2018","journal-title":"Hepatol. Commun."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1136\/gutjnl-2015-311109","article-title":"Study of hepatitis E virus infection of genotype 1 and 3 in mice with humanised liver","volume":"66","author":"Sayed","year":"2017","journal-title":"Gut"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"25482","DOI":"10.1038\/srep25482","article-title":"Convergent transcription of interferon-stimulated genes by TNF-alpha and IFN-alpha augments antiviral activity against HCV and HEV","volume":"6","author":"Wang","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"6914","DOI":"10.1073\/pnas.1705446114","article-title":"Pig model mimicking chronic hepatitis E virus infection in immunocompromised patients to assess immune correlates during chronicity","volume":"114","author":"Cao","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"7253","DOI":"10.1073\/pnas.0611506104","article-title":"Disruption of innate immunity due to mitochondrial targeting of a picornaviral protease precursor","volume":"104","author":"Yang","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"17717","DOI":"10.1073\/pnas.0508531102","article-title":"Hepatitis C virus protease NS3\/4A cleaves mitochondrial antiviral signaling protein off the mitochondria to evade innate immunity","volume":"102","author":"Li","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"11924","DOI":"10.1128\/JVI.01935-14","article-title":"Hepatitis E virus inhibits type I interferon induction by ORF1 products","volume":"88","author":"Nan","year":"2014","journal-title":"J. Virol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1908","DOI":"10.4014\/jmb.1809.09028","article-title":"Hepatitis E virus papain-like cysteine protease inhibits type I interferon induction by down-regulating melanoma differentiation-associated gene 5","volume":"28","author":"Kim","year":"2018","journal-title":"J. Microbiol. Biotechnol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.4014\/jmb.1905.05040","article-title":"Dose-dependent inhibition of melanoma differentiation-associated gene 5-mediated activation of type I interferon responses by methyltransferase of hepatitis E virus","volume":"29","author":"Myoung","year":"2019","journal-title":"J. Microbiol. Biotechnol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1007\/s12275-019-9478-8","article-title":"Methyltransferase of a cell culture-adapted hepatitis E inhibits the MDA5 receptor signaling pathway","volume":"57","author":"Myoung","year":"2019","journal-title":"J. Microbiol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1554","DOI":"10.4014\/jmb.1808.08058","article-title":"Hepatitis E virus methyltransferase inhibits type I interferon induction by targeting RIG-I","volume":"28","author":"Kang","year":"2018","journal-title":"J. Microbiol. Biotechnol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1007\/s11010-016-2715-0","article-title":"Hepatitis E virus ORF1 encoded macro domain protein interacts with light chain subunit of human ferritin and inhibits its secretion","volume":"417","author":"Ojha","year":"2016","journal-title":"Mol. Cell. Biochem."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.it.2016.11.001","article-title":"ISG15: In sickness and in health","volume":"38","author":"Hermann","year":"2017","journal-title":"Trends Immunol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1073\/pnas.0510518103","article-title":"Innate antiviral response targets HIV-1 release by the induction of ubiquitin-like protein ISG15","volume":"103","author":"Okumura","year":"2006","journal-title":"Proc. Natl. Acad Sci. USA"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"3236","DOI":"10.1099\/jgv.0.000283","article-title":"Inhibition of hepatitis C virus RNA replication by ISG15 does not require its conjugation to protein substrates by the HERC5 E3 ligase","volume":"96","author":"Domingues","year":"2015","journal-title":"J. Gen. Virol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1136\/gut.2009.195545","article-title":"The interferon stimulated gene 15 functions as a proviral factor for the hepatitis C virus and as a regulator of the IFN response","volume":"59","author":"Broering","year":"2010","journal-title":"Gut"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Sooryanarain, H., Rogers, A.J., Cao, D., Haac, M.E.R., Karpe, Y.A., and Meng, X.J. (2017). ISG15 modulates type I interferon signaling and the antiviral response during hepatitis E virus replication. J. Virol., 91.","DOI":"10.1128\/JVI.00621-17"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2088","DOI":"10.1099\/vir.0.033738-0","article-title":"Deubiquitination activity associated with hepatitis E virus putative papain-like cysteine protease","volume":"92","author":"Karpe","year":"2011","journal-title":"J. Gen. Virol."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Bagdassarian, E., Doceul, V., Pellerin, M., Demange, A., Meyer, L., Jouvenet, N., and Pavio, N. (2018). The amino-terminal region of hepatitis E virus ORF1 containing a methyltransferase (Met) and a papain-like cysteine protease (PCP) domain counteracts type I interferon response. Viruses, 10.","DOI":"10.20944\/preprints201809.0525.v1"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1038\/nature09489","article-title":"2\u2032-O methylation of the viral mRNA cap evades host restriction by IFIT family members","volume":"468","author":"Daffis","year":"2010","journal-title":"Nature"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2462","DOI":"10.1128\/JVI.02744-14","article-title":"Interferon-induced Ifit proteins: Their role in viral pathogenesis","volume":"89","author":"Fensterl","year":"2015","journal-title":"J. Virol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1099\/jgv.0.001229","article-title":"Hepatitis E virus polymerase binds to IFIT1 to protect the viral RNA from IFIT1-mediated translation inhibition","volume":"100","author":"Pingale","year":"2019","journal-title":"J. Gen. Virol."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Lin, S., Yang, Y., Nan, Y., Ma, Z., Yang, L., and Zhang, Y.J. (2019). The capsid protein of hepatitis E virus inhibits interferon induction via its N-terminal arginine-rich motif. Viruses, 11.","DOI":"10.3390\/v11111050"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"656","DOI":"10.3389\/fmicb.2020.00656","article-title":"Hepatitis E virus ORF2 inhibits RIG-I mediated interferon response","volume":"11","author":"Hingane","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"John, L., Thomas, S., Herchenroder, O., Putzer, B.M., and Schaefer, S. (2011). Hepatitis E virus ORF2 protein activates the pro-apoptotic gene CHOP and anti-apoptotic heat shock proteins. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0025378"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"8696","DOI":"10.1128\/JVI.01228-14","article-title":"Enhancement of interferon induction by ORF3 product of hepatitis E virus","volume":"88","author":"Nan","year":"2014","journal-title":"J. Virol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"27597","DOI":"10.1038\/srep27597","article-title":"The ORF3 protein of genotype 1 hepatitis E virus suppresses TLR3-induced NF-kappaB signaling via TRADD and RIP1","volume":"6","author":"He","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"8585","DOI":"10.1038\/s41598-018-26975-4","article-title":"HEV ORF3 downregulates TLR7 to inhibit the generation of type I interferon via impairment of multiple signaling pathways","volume":"8","author":"Lei","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1002\/hep.25530","article-title":"Suppression of interferon-alpha signaling by hepatitis E virus","volume":"55","author":"Dong","year":"2012","journal-title":"Hepatology"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"2173","DOI":"10.3748\/wjg.v24.i20.2173","article-title":"Effects of hepatitis E virus infection on interferon production via ISG15","volume":"24","author":"Wang","year":"2018","journal-title":"World J. Gastroenterol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1111\/jvh.12902","article-title":"Use of S17 fragment containing hepatitis E virus infectious clones in cell culture experiments: The fine print does matter","volume":"25","author":"Sridhar","year":"2018","journal-title":"J. Viral Hepat."}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/8\/3\/422\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:52:17Z","timestamp":1760176337000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/8\/3\/422"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,28]]},"references-count":100,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2020,9]]}},"alternative-id":["vaccines8030422"],"URL":"https:\/\/doi.org\/10.3390\/vaccines8030422","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,28]]}}}