nach oben

Archives of Virology

Erschienen in:

13.09.2022 | Review

Structural aspects of hepatitis E virus

verfasst von: Florencia Cancela, Ofelia Noceti, Juan Arbiza, Santiago Mirazo

Erschienen in: Archives of Virology | Ausgabe 12/2022

Einloggen, um Zugang zu erhalten

Abstract

Hepatitis E virus (HEV) is a leading cause of acute hepatitis worldwide. Hepatitis E is an enterically transmitted zoonotic disease that causes large waterborne epidemic outbreaks in developing countries and has become an increasing public-health concern in industrialized countries. In this setting, the infection is usually acute and self-limiting in immunocompetent individuals, although chronic cases in immunocompromised patients have been reported, frequently associated with several extrahepatic manifestations. Moreover, extrahepatic manifestations have also been reported in immunocompetent individuals with acute HEV infection. HEV belongs to the alphavirus-like supergroup III of single-stranded positive-sense RNA viruses, and its genome contains three partially overlapping open reading frames (ORFs). ORF1 encodes a nonstructural protein with eight domains, most of which have not been extensively characterized: methyltransferase, Y domain, papain-like cysteine protease, hypervariable region, proline-rich region, X domain, Hel domain, and RNA-dependent RNA polymerase. ORF2 and ORF3 encode the capsid protein and a multifunctional protein believed to be involved in virion release, respectively. The novel ORF4 is only expressed in HEV genotype 1 under endoplasmic reticulum stress conditions, and its exact function has not yet been elucidated. Despite important advances in recent years, the biological and molecular processes underlying HEV replication remain poorly understood, primarily due to a lack of detailed information about the functions of the viral proteins and the mechanisms involved in host-pathogen interactions. This review summarizes the current knowledge concerning HEV proteins and their biological properties, providing updated detailed data describing their function and focusing in detail on their structural characteristics. Furthermore, we review some unclear aspects of the four proteins encoded by the ORFs, highlighting the current key information gaps and discussing potential novel experimental strategies for shedding light on those issues.

Agrawal S, Gupta D, Panda SK (2001) The 3’ end of hepatitis E virus (HEV) genome binds specifically to the viral RNA-dependent RNA polymerase (RdRp). Virology 282:87–101. https://doi.org/10.1006/viro.2000.0819CrossRef

Ahola T, Karlin DG (2015) Sequence analysis reveals a conserved extension in the capping enzyme of the alphavirus supergroup, and a homologous domain in nodaviruses. Biol Direct 10:16. https://doi.org/10.1186/s13062-015-0050-0CrossRef

Anang S, Subramani C, Nair VP, Kaul S, Kaushik N, Sharma C, Tiwari A, Ranjith-Kumar CT, Surjit M (2016) Identification of critical residues in Hepatitis E virus macro domain involved in its interaction with viral methyltransferase and ORF3 proteins. Sci Rep 6:25133. https://doi.org/10.1038/srep25133CrossRef

Andrejeva J, Norsted H, Habjan M, Thiel V, Goodbourn S, Randall RE (2013) ISG56/IFIT1 is primarily responsible for interferon-induced changes to patterns of parainfluenza virus type 5 transcription and protein synthesis. J Gen Virol 94:59–68. https://doi.org/10.1099/vir.0.046797-0CrossRef

Ansari IH, Nanda SK, Durgapal H, Agrawal S, Mohanty SK, Gupta D, Jameel S, Panda SK (2000) Cloning, sequencing, and expression of the hepatitis E virus (HEV) nonstructural open reading frame 1 (ORF1). J Med Virol 60:275–283CrossRef

Bagdassarian E, Doceul V, Pellerin M, Demange A, Meyer L, Jouvenet N, 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. https://doi.org/10.3390/v10120726. Viruses 10

Bai C, Cai J, Han P, Qi J, Yuen K-Y, Wang Q (2020) The crystal structure of the emerging human-infecting hepatitis E virus E2s protein. Biochem Biophys Res Commun 532:25–31. https://doi.org/10.1016/j.bbrc.2020.07.074CrossRef

Batts W, Yun S, Hedrick R, Winton J (2011) A novel member of the family Hepeviridae from cutthroat trout (Oncorhynchus clarkii). Virus Res 158:116–123. https://doi.org/10.1016/j.virusres.2011.03.019CrossRef

Borkakoti J, Ahmed G, Rai A, Kar P (2017) Report of novel H105R, D29N, V27A mutations in the methyltransferase region of the HEV genome in patients with acute liver failure. J Clin Virol Off Publ Pan Am Soc Clin Virol 91:1–4. https://doi.org/10.1016/j.jcv.2017.03.017CrossRef

Campen A, Williams RM, Brown CJ, Meng J, Uversky VN, Dunker AK (2008) TOP-IDP-scale: a new amino acid scale measuring propensity for intrinsic disorder. Protein Pept Lett 15:956–963. https://doi.org/10.2174/092986608785849164CrossRef

Cancela F, Rendon-Marin S, Quintero-Gil C, Houston DR, Gumbis G, Panzera Y, Pérez R, Arbiza J, Mirazo S (2021) Modelling of Hepatitis E virus RNA-dependent RNA polymerase genotype 3 from a chronic patient and in silico interaction analysis by molecular docking with Ribavirin. J Biomol Struct Dyn 1–17. https://doi.org/10.1080/07391102.2021.2011416

Cao D, Huang Y-W, Meng X-J (2010) The nucleotides on the stem-loop RNA structure in the junction region of the hepatitis E virus genome are critical for virus replication. J Virol 84:13040–13044. https://doi.org/10.1128/JVI.01475-10CrossRef

Cao D, Ni Y-Y, Meng X-J (2018a) Substitution of amino acid residue V1213 in the helicase domain of the genotype 3 hepatitis E virus reduces virus replication. Virol J 15:32. https://doi.org/10.1186/s12985-018-0943-5CrossRef

Cao D, Ni Y-Y, Walker M, Huang Y-W, Meng X-J (2018b) Roles of the genomic sequence surrounding the stem-loop structure in the junction region including the 3’ terminus of open reading frame 1 in hepatitis E virus replication. J Med Virol 90:1524–1531. https://doi.org/10.1002/jmv.25215CrossRef

Cao Y-F, Tao H, Hu Y-M, Shi C-B, Wu X, Liang Q, Chi C-P, Li L, Liang Z-L, Meng J-H, Zhu F-C, Liu Z-H, Wang X-P (2017) A phase 1 randomized open-label clinical study to evaluate the safety and tolerability of a novel recombinant hepatitis E vaccine. Vaccine 35:5073–5080. https://doi.org/10.1016/j.vaccine.2017.05.072CrossRef

Chandra V, Holla P, Ghosh D, Chakrabarti D, Padigaru M, Jameel S (2011) The hepatitis E virus ORF3 protein regulates the expression of liver-specific genes by modulating localization of hepatocyte nuclear factor 4. PLoS ONE 6:e22412. https://doi.org/10.1371/journal.pone.0022412CrossRef

Chandra V, Kar-Roy A, Kumari S, Mayor S, Jameel S (2008a) The hepatitis E virus ORF3 protein modulates epidermal growth factor receptor trafficking, STAT3 translocation, and the acute-phase response. J Virol 82:7100–7110. https://doi.org/10.1128/JVI.00403-08CrossRef

Chandra V, Taneja S, Kalia M, Jameel S (2008b) Molecular biology and pathogenesis of hepatitis E virus. J Biosci 33:451–464. https://doi.org/10.1007/s12038-008-0064-1CrossRef

Cohen GB, Ren R, Baltimore D (1995) Modular binding domains in signal transduction proteins. Cell 80:237–248. https://doi.org/10.1016/0092-8674(95)90406-9CrossRef

Colson P, Decoster C (2019) Recent data on hepatitis E. Curr Opin Infect Dis 32:475–481. https://doi.org/10.1097/QCO.0000000000000590CrossRef

Córdoba L, Huang Y-W, Opriessnig T, Harral KK, Beach NM, Finkielstein CV, Emerson SU, Meng X-J (2011) Three amino acid mutations (F51L, T59A, and S390L) in the capsid protein of the hepatitis E virus collectively contribute to virus attenuation. J Virol 85:5338–5349. https://doi.org/10.1128/JVI.02278-10CrossRef

d’Azzo A, Bongiovanni A, Nastasi T (2005) E3 ubiquitin ligases as regulators of membrane protein trafficking and degradation. Traffic 6:429–441. https://doi.org/10.1111/j.1600-0854.2005.00294.xCrossRef

Debing Y, Gisa A, Dallmeier K, Pischke S, Bremer B, Manns M, Wedemeyer H, Suneetha PV, Neyts J (2014) A mutation in the hepatitis e virus RNA polymerase promotes its replication and associates with ribavirin treatment failure in organ transplant recipients. Gastroenterology 147:1008–1011. https://doi.org/10.1053/j.gastro.2014.08.040CrossRef

Debing Y, Moradpour D, Neyts J, Gouttenoire J (2016a) Update on hepatitis E virology: Implications for clinical practice. J Hepatol 65:200–212. https://doi.org/10.1016/j.jhep.2016.02.045CrossRef

Debing Y, Ramiere C, Dallmeier K, Piorkowski G, Trabaud M-A, Lebosse F, Scholtes C, Roche M, Legras-Lachuer C, de Lamballerie X, Andre P, Neyts J (2016b) Hepatitis E virus mutations associated with ribavirin treatment failure result in altered viral fitness and ribavirin sensitivity. J Hepatol 65:499–508. https://doi.org/10.1016/j.jhep.2016.05.002CrossRef

Decroly E, Ferron F, Lescar J, Canard B (2011) Conventional and unconventional mechanisms for capping viral mRNA. Nat Rev Microbiol 10:51–65. https://doi.org/10.1038/nrmicro2675CrossRef

Devhare P, Sharma K, Mhaindarkar V, Arankalle V, Lole K (2014) Analysis of helicase domain mutations in the hepatitis E virus derived from patients with fulminant hepatic failure: effects on enzymatic activities and virus replication. Virus Res 184:103–110. https://doi.org/10.1016/j.virusres.2014.02.018CrossRef

Ding Q, Heller B, Capuccino JMV, Song B, Nimgaonkar I, Hrebikova G, Contreras JE, Ploss A (2017) Hepatitis E virus ORF3 is a functional ion channel required for release of infectious particles. Proc. Natl. Acad. Sci. U. S. A. 114, 1147–1152. https://doi.org/10.1073/pnas.1614955114

Dong C, Zafrullah M, Mixson-Hayden T, Dai X, Liang J, Meng J, Kamili S (2012) Suppression of interferon-α signaling by hepatitis E virus. Hepatology 55:1324–1332. https://doi.org/10.1002/hep.25530CrossRef

Dunker AK, Oldfield CJ, Meng J, Romero P, Yang JY, Chen JW, Vacic V, Obradovic Z, Uversky VN (2008) The unfoldomics decade: an update on intrinsically disordered proteins. BMC Genomics 9(Suppl 2):S1. https://doi.org/10.1186/1471-2164-9-S2-S1CrossRef

Emerson SU, Nguyen H, Graff J, Stephany DA, Brockington A, Purcell RH (2004) In vitro replication of hepatitis E virus (HEV) genomes and of an HEV replicon expressing green fluorescent protein. J Virol 78:4838–4846. https://doi.org/10.1128/jvi.78.9.4838-4846.2004CrossRef

Fang SY, Han H (2017) Hepatitis E viral infection in solid organ transplant patients. Curr Opin Organ Transplant 22:351–355. https://doi.org/10.1097/MOT.0000000000000432CrossRef

Feld JJ, Hoofnagle JH (2005) Mechanism of action of interferon and ribavirin in treatment of hepatitis C. Nature 436:967–972. https://doi.org/10.1038/nature04082CrossRef

Finkel Y, Mizrahi O, Nachshon A, Weingarten-Gabbay S, Morgenstern D, Yahalom-Ronen Y, Tamir H, Achdout H, Stein D, Israeli O, Beth-Din A, Melamed S, Weiss S, Israely T, Paran N, Schwartz M, Stern-Ginossar N (2020) The coding capacity of SARS-CoV-2. Nature. https://doi.org/10.1038/s41586-020-2739-1CrossRef

Fu RM, Decker CC, Thi D, V.L (2019) Cell Culture Models for Hepatitis E Virus. https://doi.org/10.3390/v11070608. Viruses 11

Geng Y, Yang J, Huang W, Harrison TJ, Zhou Y, Wen Z, Wang Y (2013) Virus host protein interaction network analysis reveals that the HEV ORF3 protein may interrupt the blood coagulation process. PLoS ONE 8:e56320. https://doi.org/10.1371/journal.pone.0056320CrossRef

Gerolami R, Moal V, Colson P (2008) Chronic hepatitis E with cirrhosis in a kidney-transplant recipient. N Engl J Med. https://doi.org/10.1056/NEJMc0708687CrossRef

Gouttenoire J, Pollán A, Abrami L, Oechslin N, Mauron J, Matter M, Oppliger J, Szkolnicka D, Thi D, van der Goot VL, Moradpour FG, D (2018) Palmitoylation mediates membrane association of hepatitis E virus ORF3 protein and is required for infectious particle secretion. PLoS Pathog 14:e1007471. https://doi.org/10.1371/journal.ppat.1007471CrossRef

Gouvea V, Snellings N, Popek MJ, Longer CF, Innis BL (1998) Hepatitis E virus: complete genome sequence and phylogenetic analysis of a Nepali isolate. Virus Res 57:21–26. https://doi.org/10.1016/s0168-1702(98)00079-3CrossRef

Graff J, Nguyen H, Yu C, Elkins WR, St Claire M, Purcell RH, Emerson SU (2005) The open reading frame 3 gene of hepatitis E virus contains a cis-reactive element and encodes a protein required for infection of macaques. J Virol 79:6680–6689. https://doi.org/10.1128/JVI.79.11.6680-6689.2005CrossRef

Graff J, Torian U, Nguyen H, Emerson SU (2006) A bicistronic subgenomic mRNA encodes both the ORF2 and ORF3 proteins of hepatitis E virus. J Virol 80:5919–5926. https://doi.org/10.1128/JVI.00046-06CrossRef

Gu Y, Tang X, Zhang X, Song C, Zheng M, Wang K, Zhang J, Ng M-H, Hew C-L, Li S, Xia N, Sivaraman J (2015) Structural basis for the neutralization of hepatitis E virus by a cross-genotype antibody. Cell Res 25:604–620. https://doi.org/10.1038/cr.2015.34CrossRef

Guu TSY, Liu Z, Ye Q, Mata DA, Li K, Yin C, Zhang J, Tao YJ (2009) Structure of the hepatitis E virus-like particle suggests mechanisms for virus assembly and receptor binding. Proc. Natl. Acad. Sci. U. S. A. 106, 12992–12997. https://doi.org/10.1073/pnas.0904848106

Haglund K, Dikic I (2005) Ubiquitylation and cell signaling. EMBO J 24:3353–3359. https://doi.org/10.1038/sj.emboj.7600808CrossRef

Haldipur B, Bhukya PL, Arankalle V, Lole K (2018) Positive Regulation of Hepatitis E Virus Replication by MicroRNA-122. J Virol 92. https://doi.org/10.1128/JVI.01999-17

He M, Wang M, Huang Y, Peng W, Zheng Z, Xia N, Xu J, Tian D (2016) The ORF3 Protein of Genotype 1 Hepatitis E Virus Suppresses TLR3-induced NF-κB Signaling via TRADD and RIP1. Sci Rep 6:27597. https://doi.org/10.1038/srep27597CrossRef

He S, Miao J, Zheng Z, Wu T, Xie M, Tang M, Zhang J, Ng M-H, Xia N (2008) Putative receptor-binding sites of hepatitis E virus. J Gen Virol 89:245–249. https://doi.org/10.1099/vir.0.83308-0CrossRef

Hingane S, Joshi N, Surjit M, Ranjith-Kumar CT (2020) Hepatitis E Virus ORF2 Inhibits RIG-I Mediated Interferon Response. Front Microbiol 11:656. https://doi.org/10.3389/fmicb.2020.00656CrossRef

Holla RP, Ahmad I, Ahmad Z, Jameel S (2013) Molecular virology of hepatitis E virus. Semin. Liver Dis 33:3–14. https://doi.org/10.1055/s-0033-1338110CrossRef

Horvatits T, Zur Wiesch JS, Lütgehetmann M, Lohse AW, Pischke S (2019) The clinical perspective on hepatitis E. Viruses 11:1–19. https://doi.org/10.3390/v11070617CrossRef

Huang FF, Sun ZF, Emerson SU, Purcell RH, Shivaprasad HL, Pierson FW, Toth TE, Meng XJ (2004) Determination and analysis of the complete genomic sequence of avian hepatitis E virus (avian HEV) and attempts to infect rhesus monkeys with avian HEV. J Gen Virol 85:1609–1618. https://doi.org/10.1099/vir.0.79841-0CrossRef

Ibrahim AS, Alkhal A, Jacob J, Ghadban W, Almarri A (2009) Hepatitis E in Qatar imported by expatriate workers from Nepal: epidemiological characteristics and clinical manifestations. J Med Virol 81:1047–1051. https://doi.org/10.1002/jmv.21474CrossRef

Ingolia NT, Ghaemmaghami S, Newman JRS, Weissman JS (2009) Genome-Wide Analysis in Vivo of Resolution Using Ribosome Profiling. Science 324:218–223. https://doi.org/10.1126/science.1168978CrossRef

Jablonski SA, Morrow CD (1995) Mutation of the aspartic acid residues of the GDD sequence motif of poliovirus RNA-dependent RNA polymerase results in enzymes with altered metal ion requirements for activity. J Virol 69:1532–1539. https://doi.org/10.1128/jvi.69.3.1532-1539.1995CrossRef

Jameel S, Zafrullah M, Ozdener MH, Panda SK (1996) Expression in animal cells and characterization of the hepatitis E virus structural proteins. J Virol 70:207–216. https://doi.org/10.1128/JVI.70.1.207-216.1996CrossRef

Ji H, Chen S, He Q, Wang W, Gong S, Qian Z, Zhang Y, Wei D, Yu W, Huang F (2021) The different replication between nonenveloped and quasi-enveloped hepatitis E virus. J Med Virol 93:6267–6277. https://doi.org/10.1002/jmv.27121CrossRef

John L, Thomas S, Herchenröder O, Pützer BM, Schaefer S (2011) Hepatitis E virus ORF2 protein activates the pro-apoptotic gene CHOP and anti-apoptotic heat shock proteins. PLoS ONE 6:e25378. https://doi.org/10.1371/journal.pone.0025378CrossRef

Ju X, Xiang G, Gong M, Yang R, Qin J, Li Y, Nan Y, Yang Y, Zhang QC, Ding Q (2020) Identification of functional cis-acting RNA elements in the hepatitis E virus genome required for viral replication. PLoS Pathog 16:e1008488. https://doi.org/10.1371/journal.ppat.1008488CrossRef

Kadaré G, Haenni AL (1997) Virus-encoded RNA helicases. J Virol 71:2583–2590. https://doi.org/10.1128/JVI.71.4.2583-2590.1997CrossRef

Kalia M, Chandra V, Rahman SA, Sehgal D, Jameel S (2009) Heparan sulfate proteoglycans are required for cellular binding of the hepatitis E virus ORF2 capsid protein and for viral infection. J Virol 83:12714–12724. https://doi.org/10.1128/JVI.00717-09CrossRef

Kanade GD, Pingale KD, Karpe YA (2019) Protein Interactions Network of Hepatitis E Virus RNA and Polymerase With Host Proteins. Front Microbiol 10:2501. https://doi.org/10.3389/fmicb.2019.02501CrossRef

Kanade GD, Pingale KD, Karpe YA (2018) Activities of Thrombin and Factor Xa Are Essential for Replication of Hepatitis E Virus and Are Possibly Implicated in ORF1 Polyprotein Processing. J Virol 92. https://doi.org/10.1128/JVI.01853-17

Kang S, Choi C, Choi I, Han K-N, Rho SW, Choi J, Kwon J, Park M-K, Kim S-J, Myoung J (2018) Hepatitis E Virus Methyltransferase Inhibits Type I Interferon Induction by Targeting RIG-I. J Microbiol Biotechnol 28:1554–1562. https://doi.org/10.4014/jmb.1808.08058CrossRef

Kang S, Myoung J (2017a) Host Innate Immunity against Hepatitis E Virus and Viral Evasion Mechanisms. J Microbiol Biotechnol 27:1727–1735. https://doi.org/10.4014/jmb.1708.08045CrossRef

Kang S, Myoung J (2017b) Primary lymphocyte infection models for KSHV and its putative tumorigenesis mechanisms in B cell lymphomas. J Microbiol 55:319–329. https://doi.org/10.1007/s12275-017-7075-2CrossRef

Kannan H, Fan S, Patel D, Bossis I, Zhang Y-J (2009) The hepatitis E virus open reading frame 3 product interacts with microtubules and interferes with their dynamics. J Virol 83:6375–6382. https://doi.org/10.1128/JVI.02571-08CrossRef

Kar-Roy A, Korkaya H, Oberoi R, Lal SK, Jameel S (2004) The hepatitis E virus open reading frame 3 protein activates ERK through binding and inhibition of the MAPK phosphatase. J Biol Chem 279:28345–28357. https://doi.org/10.1074/jbc.M400457200CrossRef

Karpe YA, Lole KS (2011) Deubiquitination activity associated with hepatitis E virus putative papain-like cysteine protease. J Gen Virol 92:2088–2092. https://doi.org/10.1099/vir.0.033738-0CrossRef

Karpe YA, Lole KS (2010a) NTPase and 5’ to 3’ RNA duplex-unwinding activities of the hepatitis E virus helicase domain. J Virol 84:3595–3602. https://doi.org/10.1128/JVI.02130-09CrossRef

Karpe YA, Lole KS (2010b) RNA 5’-triphosphatase activity of the hepatitis E virus helicase domain. J Virol 84:9637–9641. https://doi.org/10.1128/JVI.00492-10CrossRef

Kay BK, Williamson MP, Sudol M (2000) The importance of being proline: the interaction of proline-rich motifs in signaling proteins with their cognate domains. FASEB J Off Publ Fed Am Soc Exp Biol 14:231–241

Kenney SP, Meng X-J (2015) 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. J Virol 89:3793–3803. https://doi.org/10.1128/JVI.03582-14CrossRef

Kim E, Myoung J (2018) Hepatitis E Virus Papain-Like Cysteine Protease Inhibits Type I Interferon Induction by Down-Regulating Melanoma Differentiation-Associated Gene 5. J Microbiol Biotechnol 28:1908–1915. https://doi.org/10.4014/jmb.1809.09028CrossRef

Koonin EV, Dolja VV (1993) Evolution and taxonomy of positive-strand RNA viruses: implications of comparative analysis of amino acid sequences. Crit Rev Biochem Mol Biol 28:375–430. https://doi.org/10.3109/10409239309078440CrossRef

Koonin EV, Gorbalenya AE, Purdy MA, Rozanov MN, Reyes GR, Bradley DW (1992) 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. Proc. Natl. Acad. Sci. U. S. A. 89, 8259–8263. https://doi.org/10.1073/pnas.89.17.8259

Korkaya H, Jameel S, Gupta D, Tyagi S, Kumar R, Zafrullah M, Mazumdar M, Lal SK, Xiaofang L, Sehgal D, Das SR, Sahal D (2001) The ORF3 protein of hepatitis E virus binds to Src homology 3 domains and activates MAPK. J Biol Chem 276:42389–42400. https://doi.org/10.1074/jbc.M101546200CrossRef

Kumar M, Hooda P, Khanna M, Patel U, Sehgal D (2020) Development of BacMam Induced Hepatitis E Virus Replication Model in Hepatoma Cells to Study the Polyprotein Processing. Front Microbiol 11:1347. https://doi.org/10.3389/fmicb.2020.01347CrossRef

Kumar S, Subhadra S, Singh B, Panda BK (2013) Hepatitis E virus: the current scenario. Int J Infect Dis 17:e228–e233. https://doi.org/10.1016/j.ijid.2012.11.026CrossRef

Legrand-Abravanel F, Mansuy JM, Dubois M, Kamar N, Peron JM, Rostaing L, Izopet J (2009) Hepatitis E virus genotype 3 diversity. France Emerg Infect Dis 15:110–114. https://doi.org/10.3201/eid1501.080296CrossRef

Lhomme S, Abravanel F, Dubois M, Sandres-saune K, Mansuy J, Rostaing L, Kamar N, Izopet J (2014a) Characterization of the Polyproline Region of the Hepatitis E Virus in. J Virol 88:12017–12025. https://doi.org/10.1128/JVI.01625-14CrossRef

Lhomme S, Garrouste C, Kamar N, Dubois M, Rostaing L, Izopet J (2014b) Influence of Polyproline Region and Macro Domain Genetic Heterogeneity on HEV Persistence in Immunocompromised Patients. J Infect Dis 209:300–303. https://doi.org/10.1093/infdis/jit438CrossRef

Lhomme S, Migueres M, Abravanel F, Marion O, Kamar N, Izopet J (2020a) Hepatitis E Virus: How It Escapes Host Innate Immunity. Vaccines 8. https://doi.org/10.3390/vaccines8030422

Lhomme S, Nicot F, Jeanne N, Dimeglio C, Roulet A, Lefebvre C, Carcenac R, Manno M, Dubois M, Peron J-M, Alric L, Kamar N, Abravanel F, Izopet J (2020b) Insertions and Duplications in the Polyproline Region of the Hepatitis E Virus. Front Microbiol 11:1. https://doi.org/10.3389/fmicb.2020.00001CrossRef

Li C, Debing Y, Jankevicius G, Neyts J, Ahel I, Coutard B, Canard B (2016) Viral Macro Domains Reverse Protein ADP-Ribosylation. J Virol 90:8478–8486. https://doi.org/10.1128/JVI.00705-16CrossRef

Li H, Zheng Z, Zhou P, Zhang B, Shi Z, Hu Q, Wang H (2010) The cysteine protease domain of porcine reproductive and respiratory syndrome virus non-structural protein 2 antagonizes interferon regulatory factor 3 activation. J Gen Virol 91:2947–2958. https://doi.org/10.1099/vir.0.025205-0CrossRef

Li P, Li Y, Wang, Yijin, Liu J, Lavrijsen M, Li, Yang, Zhang R, Verstegen MMA, Wang Y, Li T-C, Ma Z, Kainov DE, Bruno MJ, de Man RA, van der Laan LJW, Peppelenbosch MP, Pan Q (2022) Recapitulating hepatitis E virus-host interactions and facilitating antiviral drug discovery in human liver-derived organoids. Sci Adv 8:eabj5908. https://doi.org/10.1126/sciadv.abj5908CrossRef

Li S-W, Zhao Q, Wu T, Chen S, Zhang J, Xia N-S (2015) The development of a recombinant hepatitis E vaccine HEV 239. Hum Vaccin Immunother 11:908–914. https://doi.org/10.1080/21645515.2015.1008870CrossRef

Li S, Tang X, Seetharaman J, Yang C, Gu Y, Zhang J, Du H, Shih JWK, Hew C-L, Sivaraman J, Xia N (2009) Dimerization of hepatitis E virus capsid protein E2s domain is essential for virus-host interaction. PLoS Pathog 5:e1000537. https://doi.org/10.1371/journal.ppat.1000537CrossRef

Li T-C, Kataoka M, Takahashi K, Yoshizaki S, Kato T, Ishii K, Takeda N, Mishiro S, Wakita T (2015) Generation of hepatitis E virus-like particles of two new genotypes G5 and G6 and comparison of antigenic properties with those of known genotypes. Vet Microbiol 178:150–157. https://doi.org/10.1016/j.vetmic.2015.04.020CrossRef

Li T-C, Suzaki Y, Ami Y, Dhole TN, Miyamura T, Takeda N (2004) Protection of cynomolgus monkeys against HEV infection by oral administration of recombinant hepatitis E virus-like particles. Vaccine 22:370–377. https://doi.org/10.1016/j.vaccine.2003.08.004CrossRef

Li T-C, Takeda N, Miyamura T, Matsuura Y, Wang JCY, Engvall H, Hammar L, Xing L, Cheng RH (2005) Essential elements of the capsid protein for self-assembly into empty virus-like particles of hepatitis E virus. J Virol 79:12999–13006. https://doi.org/10.1128/JVI.79.20.12999-13006.2005CrossRef

Li TC, Yamakawa Y, Suzuki K, Tatsumi M, Razak MA, Uchida T, Takeda N, Miyamura T (1997) Expression and self-assembly of empty virus-like particles of hepatitis E virus. J Virol 71:7207–7213. https://doi.org/10.1128/JVI.71.10.7207-7213.1997CrossRef

Li Y, Qu C, Yu P, Ou X, Pan Q, Wang W (2019) The Interplay between Host Innate Immunity and Hepatitis E Virus. https://doi.org/10.3390/v11060541. Viruses 11

Lin S, Yang Y, Nan Y, Ma Z, Yang L, Zhang Y-J (2019) The Capsid Protein of Hepatitis E Virus Inhibits Interferon Induction via Its N-terminal Arginine-Rich Motif. https://doi.org/10.3390/v11111050. Viruses 11

Liu H, Fu Y, Jiang D, Li G, Xie J, Peng Y, Yi X, Ghabrial SA (2009) A novel mycovirus that is related to the human pathogen hepatitis E virus and rubi-like viruses. J Virol 83:1981–1991. https://doi.org/10.1128/JVI.01897-08CrossRef

Loo Y-M, Fornek J, Crochet N, Bajwa G, Perwitasari O, Martinez-Sobrido L, Akira S, Gill MA, García-Sastre A, Katze MG, Gale MJ (2008) Distinct RIG-I and MDA5 signaling by RNA viruses in innate immunity. J Virol 82:335–345. https://doi.org/10.1128/JVI.01080-07CrossRef

Ma Y, Lin S-Q, Gao Y, Li M, Luo W-X, Zhang J, Xia N-S (2003) Expression of ORF2 partial gene of hepatitis E virus in tomatoes and immunoactivity of expression products. World J Gastroenterol 9:2211–2215. https://doi.org/10.3748/wjg.v9.i10.2211CrossRef

Magden J, Takeda N, Li T, Auvinen P, Ahola T, Miyamura T, Merits A, Kääriäinen L (2001) Virus-specific mRNA capping enzyme encoded by hepatitis E virus. J Virol 75:6249–6255. https://doi.org/10.1128/JVI.75.14.6249-6255.2001CrossRef

Mahilkar S, Paingankar MS, Lole KS (2016) Hepatitis E virus RNA-dependent RNA polymerase: RNA template specificities, recruitment and synthesis. J Gen Virol 97:2231–2242. https://doi.org/10.1099/jgv.0.000528CrossRef

Maloney BJ, Takeda N, Suzaki Y, Ami Y, Li TC, Miyamura T, Arntzen CJ, Mason HS (2005) Challenges in creating a vaccine to prevent hepatitis E. Vaccine 23:1870–1874. https://doi.org/10.1016/j.vaccine.2004.11.020CrossRef

Mazalovska M, Varadinov N, Koynarski T, Minkov I, Teoharov P, Lomonossoff GP, Zahmanova G (2017) Detection of Serum Antibodies to Hepatitis E Virus Based on HEV Genotype 3 ORF2 Capsid Protein Expressed in Nicotiana benthamiana. Ann Lab Med 37:313–319. https://doi.org/10.3343/alm.2017.37.4.313CrossRef

Mendoza-Lopez C, Lopez-Lopez P, Atienza-Ayala S, Rivero-Juarez A, Benito R (2020) Parsonage-Turner syndrome associated with hepatitis E infection in immunocompetent patients. Virus Res 290:198165. https://doi.org/10.1016/j.virusres.2020.198165CrossRef

Mhaindarkar V, Sharma K, Lole KS (2014) Mutagenesis of hepatitis E virus helicase motifs: effects on enzyme activity. Virus Res 179:26–33. https://doi.org/10.1016/j.virusres.2013.11.022CrossRef

Mishra N, Walimbe AM, Arankalle VA (2013) Hepatitis E virus from India exhibits significant amino acid mutations in fulminant hepatic failure patients. Virus Genes 46:47–53. https://doi.org/10.1007/s11262-012-0833-7CrossRef

Moin SM, Chandra V, Arya R, Jameel S (2009) The hepatitis E virus ORF3 protein stabilizes HIF-1alpha and enhances HIF-1-mediated transcriptional activity through p300/CBP. Cell Microbiol 11:1409–1421. https://doi.org/10.1111/j.1462-5822.2009.01340.xCrossRef

Moin SM, Panteva M, Jameel S (2007) The hepatitis E virus Orf3 protein protects cells from mitochondrial depolarization and death. J Biol Chem 282:21124–21133. https://doi.org/10.1074/jbc.M701696200CrossRef

Montpellier C, Wychowski C, Sayed IM, Meunier J-C, Saliou J-M, Ankavay M, Bull A, Pillez A, Abravanel F, Helle F, Brochot E, Drobecq H, Farhat R, Aliouat-Denis C-M, Haddad JG, Izopet J, Meuleman P, Goffard A, Dubuisson J, Cocquerel L (2018) Hepatitis E Virus Lifecycle and Identification of 3 Forms of the ORF2 Capsid Protein. Gastroenterology 154:211–223e8. https://doi.org/10.1053/j.gastro.2017.09.020CrossRef

Mori Y, Matsuura Y (2011) Structure of hepatitis E viral particle. Virus Res 161:59–64. https://doi.org/10.1016/j.virusres.2011.03.015CrossRef

Muñoz-Chimeno M, Cenalmor A, Garcia-Lugo MA, Hernandez M, Rodriguez-Lazaro D, Avellon A (2020) Proline-Rich Hypervariable Region of Hepatitis E Virus: Arranging the Disorder. Microorganisms 8. https://doi.org/10.3390/microorganisms8091417

Myoung J, Lee JY, Min KS (2019) Methyltransferase of a cell culture-adapted hepatitis E inhibits the MDA5 receptor signaling pathway. J Microbiol 57:1126–1131. https://doi.org/10.1007/s12275-019-9478-8CrossRef

Nagashima S, Takahashi M, Jirintai S, Tanaka T, Nishizawa T, Yasuda J, Okamoto H (2011a) Tumour susceptibility gene 101 and the vacuolar protein sorting pathway are required for the release of hepatitis E virions. J Gen Virol 92:2838–2848. https://doi.org/10.1099/vir.0.035378-0CrossRef

Nagashima S, Takahashi M, Jirintai S, Tanggis, Kobayashi T, Nishizawa T, Okamoto H (2014) The membrane on the surface of hepatitis E virus particles is derived from the intracellular membrane and contains trans-Golgi network protein 2. Arch Virol 159:979–991. https://doi.org/10.1007/s00705-013-1912-3CrossRef

Nagashima S, Takahashi M, Jirintai, Tanaka T, Yamada K, Nishizawa T, Okamoto H (2011b) A PSAP motif in the ORF3 protein of hepatitis E virus is necessary for virion release from infected cells. J Gen Virol 92:269–278. https://doi.org/10.1099/vir.0.025791-0CrossRef

Nair VP, Anang S, Subramani C, Madhvi A, Bakshi K, Srivastava A, Shalimar, Nayak B, Kumar R, Surjit CT, M (2016) Endoplasmic Reticulum Stress Induced Synthesis of a Novel Viral Factor Mediates Efficient Replication of Genotype-1 Hepatitis E Virus. PLoS Pathog 12:e1005521. https://doi.org/10.1371/journal.ppat.1005521CrossRef

Nan Y, Ma Z, Wang R, Yu Y, Kannan H, Fredericksen B, Zhang Y-J (2014a) Enhancement of interferon induction by ORF3 product of hepatitis E virus. J Virol 88:8696–8705. https://doi.org/10.1128/JVI.01228-14CrossRef

Nan Y, Yu Y, Ma Z, Khattar SK, Fredericksen B, Zhang Y-J (2014b) Hepatitis E virus inhibits type I interferon induction by ORF1 products. J Virol 88:11924–11932. https://doi.org/10.1128/JVI.01935-14CrossRef

Nan Y, Zhang Y-J (2016) Molecular Biology and Infection of Hepatitis E Virus. Front Microbiol 7:1419. https://doi.org/10.3389/fmicb.2016.01419CrossRef

Narayanan S, Abutaleb A, Sherman KE, Kottilil S (2019) Clinical features and determinants of chronicity in hepatitis E virus infection. J Viral Hepat 26:414–421. https://doi.org/10.1111/jvh.13059CrossRef

Nguyen HT, Torian U, Faulk K, Mather K, Engle RE, Thompson E, Bonkovsky HL, Emerson SU (2012) 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. J Gen Virol 93:526–530. https://doi.org/10.1099/vir.0.037259-0CrossRef

Ojha NK, Lole KS (2016) Hepatitis E virus ORF1 encoded macro domain protein interacts with light chain subunit of human ferritin and inhibits its secretion. Mol Cell Biochem 417:75–85. https://doi.org/10.1007/s11010-016-2715-0CrossRef

Osterman A, Stellberger T, Gebhardt A, Kurz M, Friedel CC, Uetz P, Nitschko H, Baiker A, Vizoso-Pinto MG (2015) The Hepatitis E virus intraviral interactome. Sci Rep 5:13872. https://doi.org/10.1038/srep13872CrossRef

Paliwal D, Panda SK, Kapur N, Varma SPK, Durgapal H (2014) Hepatitis E virus (HEV) protease: a chymotrypsin-like enzyme that processes both non-structural (pORF1) and capsid (pORF2) protein. J Gen Virol 95:1689–1700. https://doi.org/10.1099/vir.0.066142-0CrossRef

Palta S, Saroa R, Palta A (2014) Overview of the coagulation system. Indian J Anaesth 58:515–523. https://doi.org/10.4103/0019-5049.144643CrossRef

Park S, Bin (2012) Hepatitis E vaccine debuts. Nature. https://doi.org/10.1038/491021aCrossRef

Parvez MK (2017a) Mutational analysis of hepatitis E virus ORF1 “Y-domain”: Effects on RNA replication and virion infectivity. World J Gastroenterol 23:590–602. https://doi.org/10.3748/wjg.v23.i4.590CrossRef

Parvez MK (2017b) The hepatitis E virus nonstructural polyprotein. Future Microbiol 12:915–924. https://doi.org/10.2217/fmb-2017-0016CrossRef

Parvez MK (2015a) The intergenic-junction variant (genotype 2 isolate) of hepatitis E virus restores the CREX “stem-loop” structural integrity, essential for viral life cycle. Gene 559:149–154. https://doi.org/10.1016/j.gene.2015.01.033CrossRef

Parvez MK (2015b) The hepatitis E virus ORF1 “X-domain” residues form a putative macrodomain protein/Appr-1″-pase catalytic-site, critical for viral RNA replication. Gene 566:47–53. https://doi.org/10.1016/j.gene.2015.04.026CrossRef

Parvez MK (2013) Molecular characterization of hepatitis E virus ORF1 gene supports a papain-like cysteine protease (PCP)-domain activity. Virus Res 178:553–556. https://doi.org/10.1016/j.virusres.2013.07.020CrossRef

Parvez MK, Al-Dosari MS (2015) Evidence of MAPK-JNK1/2 activation by hepatitis E virus ORF3 protein in cultured hepatoma cells. Cytotechnology 67:545–550. https://doi.org/10.1007/s10616-014-9785-1CrossRef

Parvez MK, Khan AA (2014) Molecular modeling and analysis of hepatitis E virus (HEV) papain-like cysteine protease. Virus Res 179:220–224. https://doi.org/10.1016/j.virusres.2013.11.016CrossRef

Parvez MK, Subbarao N (2018) Molecular Analysis and Modeling of Hepatitis E Virus Helicase and Identification of Novel Inhibitors by Virtual Screening. Biomed Res. Int. 2018, 5753804. https://doi.org/10.1155/2018/5753804

Pawson T (1995) Protein modules and signalling networks. Nature 373:573–580. https://doi.org/10.1038/373573a0CrossRef

Perttilä J, Spuul P, Ahola T (2013) Early secretory pathway localization and lack of processing for hepatitis E virus replication protein pORF1. J Gen Virol 94:807–816. https://doi.org/10.1099/vir.0.049577-0CrossRef

Pingale KD, Kanade GD, Karpe YA (2019) Hepatitis E virus polymerase binds to IFIT1 to protect the viral RNA from IFIT1-mediated translation inhibition. J Gen Virol 100:471–483. https://doi.org/10.1099/jgv.0.001229CrossRef

Pischke S, Suneetha PV, Baechlein C, Barg-Hock H, Heim A, Kamar N, Schlue J, Strassburg CP, Lehner F, Raupach R, Bremer B, Magerstedt P, Cornberg M, Seehusen F, Baumgaertner W, Klempnauer J, Izopet J, Manns MP, Grummer B, Wedemeyer H (2010) Hepatitis E virus infection as a cause of graft hepatitis in liver transplant recipients. Liver Transpl Off Publ Am Assoc Study Liver Dis Int Liver Transpl Soc 16:74–82. https://doi.org/10.1002/lt.21958CrossRef

Proudfoot A, Hyrina A, Holdorf M, Frank AO, Bussiere D (2019) First Crystal Structure of a Nonstructural Hepatitis E Viral Protein Identifies a Putative Novel Zinc-Binding Protein. J Virol 93. https://doi.org/10.1128/JVI.00170-19

Pudupakam RS, Huang YW, Opriessnig T, Halbur PG, Pierson FW, Meng XJ (2009) 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. J Virol 83:384–395. https://doi.org/10.1128/JVI.01854-08CrossRef

Pudupakam RS, Kenney SP, Córdoba L, Huang Y-W, Dryman BA, Leroith T, Pierson FW, Meng X-J (2011) Mutational analysis of the hypervariable region of hepatitis e virus reveals its involvement in the efficiency of viral RNA replication. J Virol 85:10031–10040. https://doi.org/10.1128/JVI.00763-11CrossRef

Purdy MA (2012) Evolution of the hepatitis E virus polyproline region: order from disorder. J Virol 86:10186–10193. https://doi.org/10.1128/JVI.01374-12CrossRef

Purdy MA, Lara J, Khudyakov YE (2012) The hepatitis E virus polyproline region is involved in viral adaptation. PLoS ONE 7:e35974. https://doi.org/10.1371/journal.pone.0035974CrossRef

Radivojac P, Iakoucheva LM, Oldfield CJ, Obradovic Z, Uversky VN, Dunker AK (2007) Intrinsic disorder and functional proteomics. Biophys J 92:1439–1456. https://doi.org/10.1529/biophysj.106.094045CrossRef

Ratra R, Kar-Roy A, Lal SK (2009) ORF3 protein of hepatitis E virus interacts with the Bbeta chain of fibrinogen resulting in decreased fibrinogen secretion from HuH-7 cells. J Gen Virol 90:1359–1370. https://doi.org/10.1099/vir.0.009274-0CrossRef

Ratra R, Kar-Roy A, Lal SK (2008) The ORF3 protein of hepatitis E virus interacts with hemopexin by means of its 26 amino acid N-terminal hydrophobic domain II. Biochemistry 47:1957–1969. https://doi.org/10.1021/bi7016552CrossRef

Rehman S, Kapur N, Durgapal H, Panda SK (2008) Subcellular localization of hepatitis E virus (HEV) replicase. Virology 370:77–92. https://doi.org/10.1016/j.virol.2007.07.036CrossRef

Reyes-Turcu FE, Ventii KH, Wilkinson KD (2009) Regulation and cellular roles of ubiquitin-specific deubiquitinating enzymes. Annu Rev Biochem 78:363–397. https://doi.org/10.1146/annurev.biochem.78.082307.091526CrossRef

Rozanov MN, Koonin EV, Gorbalenya AE (1992) Conservation of the putative methyltransferase domain: a hallmark of the “Sindbis-like” supergroup of positive-strand RNA viruses. J Gen Virol 73(Pt 8):2129–2134. https://doi.org/10.1099/0022-1317-73-8-2129CrossRef

Saraswat S, Chaudhary M, Sehgal D (2019) Hepatitis E Virus Cysteine Protease Has Papain Like Properties Validated by in silico Modeling and Cell-Free Inhibition Assays. Front Cell Infect Microbiol 9:478. https://doi.org/10.3389/fcimb.2019.00478CrossRef

Sayed IM, Elkhawaga AA, El-Mokhtar MA (2019) In vivo models for studying Hepatitis E virus infection; Updates and applications. Virus Res 274:197765. https://doi.org/10.1016/j.virusres.2019.197765CrossRef

Sayed IM, Meuleman P (2019) Updates in Hepatitis E virus (HEV) field; lessons learned from human liver chimeric mice. Rev. Med. Virol. e2086. https://doi.org/10.1002/rmv.2086

Scholz J, Falkenhagen A, Johne R (2021) The Translated Amino Acid Sequence of an Insertion in the Hepatitis E Virus Strain 47832c Genome, But Not the RNA Sequence, Is Essential for Efficient Cell Culture Replication. Viruses 13. https://doi.org/10.3390/v13050762

Sehgal D, Thomas S, Chakraborty M, Jameel S (2006) Expression and processing of the Hepatitis E virus ORF1 nonstructural polyprotein. Virol J 3:38. https://doi.org/10.1186/1743-422X-3-38CrossRef

Shafat Z, Ahmed A, Parvez MK, Parveen S (2022) Analysis of codon usage patterns in open reading frame 4 of hepatitis E viruses. Beni-Suef Univ J basic Appl Sci 11:65. https://doi.org/10.1186/s43088-022-00244-wCrossRef

Shafat Z, Ahmed A, Parvez MK, Parveen S (2021) Sequence to structure analysis of the ORF4 protein from Hepatitis E virus. Bioinformation 17:818–828. https://doi.org/10.6026/97320630017818CrossRef

Shukla P, Nguyen HT, Faulk K, Mather K, Torian U, Engle RE, Emerson SU (2012) Adaptation of a genotype 3 hepatitis E virus to efficient growth in cell culture depends on an inserted human gene segment acquired by recombination. J Virol 86:5697–5707. https://doi.org/10.1128/JVI.00146-12CrossRef

Smith DB, Simmonds P (2015) Hepatitis E virus and fulminant hepatitis–a virus or host-specific pathology? Liver Int. Off J Int Assoc Study Liver 35:1334–1340. https://doi.org/10.1111/liv.12629CrossRef

Smith DB, Simmonds P, Jameel S, Emerson SU, Harrison TJ, Meng X-J, Okamoto H, Van der Poel WHM, Purdy MA (2014) Consensus proposals for classification of the family Hepeviridae. J Gen Virol 95:2223–2232. https://doi.org/10.1099/vir.0.068429-0CrossRef

Smith DB, Vanek J, Ramalingam S, Johannessen I, Templeton K, Simmonds P (2012) Evolution of the hepatitis E virus hypervariable region. J Gen Virol 93:2408–2418. https://doi.org/10.1099/vir.0.045351-0CrossRef

Sridhar S, Yip CCY, Wu S, Cai J, Zhang AJ-X, Leung K-H, Chung TWH, Chan JFW, Chan W-M, Teng JLL, Au-Yeung RKH, Cheng VCC, Chen H, Lau SKP, Woo PCY, Xia N-S, Lo C-M, Yuen K-Y (2018) Rat Hepatitis E Virus as Cause of Persistent Hepatitis after Liver Transplant. Emerg Infect Dis 24:2241–2250. https://doi.org/10.3201/eid2412.180937CrossRef

Stern-Ginossar N (2015) Decoding Viral Infection by Ribosome Profiling. J Virol 89:6164–6166. https://doi.org/10.1128/jvi.02528-14CrossRef

Strauss JH, Strauss EG (1994) The alphaviruses: gene expression, replication, and evolution. Microbiol Rev 58:491–562. https://doi.org/10.1128/mr.58.3.491-562.1994CrossRef

Subramani C, Nair VP, Anang S, Mandal S, Das, Pareek M, Kaushik N, Srivastava A, Saha S, Shalimar, Nayak B, Ranjith-Kumar CT, Surjit M (2018) Host-Virus Protein Interaction Network Reveals the Involvement of Multiple Host Processes in the Life Cycle of Hepatitis E Virus. mSystems 3 https://doi.org/10.1128/mSystems.00135-17

Sun Z, Chen Z, Lawson SR, Fang Y (2010) The cysteine protease domain of porcine reproductive and respiratory syndrome virus nonstructural protein 2 possesses deubiquitinating and interferon antagonism functions. J Virol 84:7832–7846. https://doi.org/10.1128/JVI.00217-10CrossRef

Suppiah S, Zhou Y, Frey TK (2011) Lack of processing of the expressed ORF1 gene product of hepatitis E virus. Virol J 8:245. https://doi.org/10.1186/1743-422X-8-245CrossRef

Surjit M, Jameel S, Lal SK (2007) Cytoplasmic localization of the ORF2 protein of hepatitis E virus is dependent on its ability to undergo retrotranslocation from the endoplasmic reticulum. J Virol 81:3339–3345. https://doi.org/10.1128/JVI.02039-06CrossRef

Surjit M, Oberoi R, Kumar R, Lal SK (2006) Enhanced alpha1 microglobulin secretion from Hepatitis E virus ORF3-expressing human hepatoma cells is mediated by the tumor susceptibility gene 101. J Biol Chem 281:8135–8142. https://doi.org/10.1074/jbc.M509568200CrossRef

Surjit M, Varshney B, Lal SK (2012) The ORF2 glycoprotein of hepatitis E virus inhibits cellular NF-κB activity by blocking ubiquitination mediated proteasomal degradation of IκBα in human hepatoma cells. BMC Biochem 13:7. https://doi.org/10.1186/1471-2091-13-7CrossRef

Takahashi K, Okamoto H, Abe N, Kawakami M, Matsuda H, Mochida S, Sakugawa H, Suginoshita Y, Watanabe S, Yamamoto K, Miyakawa Y, Mishiro S (2009) Virulent strain of hepatitis E virus genotype 3, Japan. Emerg Infect Dis 15:704–709. https://doi.org/10.3201/eid1505.081100CrossRef

Takahashi M, Yamada K, Hoshino Y, Takahashi H, Ichiyama K, Tanaka T, Okamoto H (2008) Monoclonal antibodies raised against the ORF3 protein of hepatitis E virus (HEV) can capture HEV particles in culture supernatant and serum but not those in feces. Arch Virol 153:1703–1713. https://doi.org/10.1007/s00705-008-0179-6CrossRef

Takeuchi O, Akira S (2010) Pattern recognition receptors and inflammation. Cell 140:805–820. https://doi.org/10.1016/j.cell.2010.01.022CrossRef

Tang X, Yang C, Gu Y, Song C, Zhang X, Wang Y, Zhang J, Hew CL, Li S, Xia N, Sivaraman J (2011) Structural basis for the neutralization and genotype specificity of hepatitis E virus. Proc. Natl. Acad. Sci. U. S. A. 108, 10266–10271. https://doi.org/10.1073/pnas.1101309108

Todt D, Friesland M, Moeller N, Praditya D, Kinast V, Brüggemann Y, Knegendorf L, Burkard T, Steinmann J, Burm R, Verhoye L, Wahid A, Meister TL, Engelmann M, Pfankuche VM, Puff C, Vondran FWR, Baumgärtner W, Meuleman P, Behrendt P, Steinmann E (2020) Robust hepatitis E virus infection and transcriptional response in human hepatocytes. Proc. Natl. Acad. Sci. U. S. A. 117, 1731–1741. https://doi.org/10.1073/pnas.1912307117

Todt D, Gisa A, Radonic A, Nitsche A, Behrendt P, Suneetha PV, Pischke S, Bremer B, Brown RJP, Manns MP, Cornberg M, Bock CT, Steinmann E, Wedemeyer H (2016a) In vivo evidence for ribavirin-induced mutagenesis of the hepatitis E virus genome. Gut 65:1733–1743. https://doi.org/10.1136/gutjnl-2015-311000CrossRef

Todt D, Walter S, Brown RJP, Steinmann E (2016b) Mutagenic Effects of Ribavirin on Hepatitis E Virus-Viral Extinction versus Selection of Fitness-Enhancing Mutations. Viruses 8. https://doi.org/10.3390/v8100283

Tsai CJ, Ma B, Sham YY, Kumar S, Nussinov R (2001) Structured disorder and conformational selection. Proteins 44:418–427. https://doi.org/10.1002/prot.1107CrossRef

Tyagi S, Korkaya H, Zafrullah M, Jameel S, Lal SK (2002) The phosphorylated form of the ORF3 protein of hepatitis E virus interacts with its non-glycosylated form of the major capsid protein, ORF2. J Biol Chem 277:22759–22767. https://doi.org/10.1074/jbc.M200185200CrossRef

van der Heijden MW, Bol JF (2002) Composition of alphavirus-like replication complexes: involvement of virus and host encoded proteins. Arch Virol 147:875–898. https://doi.org/10.1007/s00705-001-0773-3CrossRef

van der Poel WH, Verschoor F, van der Heide R, Herrera MI, Vivo A, Kooreman M, de Roda Husman AM (2001) Hepatitis E virus sequences in swine related to sequences in humans, The Netherlands. Emerg Infect Dis 7:970–976. https://doi.org/10.3201/eid0706.010608CrossRef

Vázquez AL, Alonso JM, Parra F (2000) Mutation analysis of the GDD sequence motif of a calicivirus RNA-dependent RNA polymerase. J Virol 74:3888–3891. https://doi.org/10.1128/jvi.74.8.3888-3891.2000CrossRef

Vikram T, Kumar P (2018) Analysis of Hepatitis E virus (HEV) X-domain structural model. Bioinformation 14:398–403. https://doi.org/10.6026/97320630014398CrossRef

Villarroya-Beltri C, Guerra S, Sánchez-Madrid F (2017) ISGylation - a key to lock the cell gates for preventing the spread of threats. J Cell Sci 130:2961–2969. https://doi.org/10.1242/jcs.205468CrossRef

Wang B, Meng X-J (2021) Structural and molecular biology of hepatitis E virus. Comput Struct Biotechnol J 19:1907–1916. https://doi.org/10.1016/j.csbj.2021.03.038CrossRef

Wang C, Guo L, Yu D, Hua X, Yang Z, Yuan C, Cui L (2014) HEV-ORF3 Encoding Phosphoprotein Interacts With Hepsin. Hepat Mon 14:e13902. https://doi.org/10.5812/hepatmon.13902CrossRef

Wang X, Gillam S (2001) Mutations in the GDD motif of rubella virus putative RNA-dependent RNA polymerase affect virus replication. Virology 285:322–331. https://doi.org/10.1006/viro.2001.0939CrossRef

Wang X, Zhao Q, Dang L, Sun Y, Gao J, Liu B, Syed SF, Tao H, Zhang G, Luo J, Zhou E-M (2015) Characterization of Two Novel Linear B-Cell Epitopes in the Capsid Protein of Avian Hepatitis E Virus (HEV) That Are Common to Avian, Swine, and Human HEVs. J Virol 89:5491–5501. https://doi.org/10.1128/JVI.00107-15CrossRef

Webb GW, Dalton HR (2019) Hepatitis E: an underestimated emerging threat. Ther Adv Infect Dis 6:2049936119837162. https://doi.org/10.1177/2049936119837162CrossRef

Welchman RL, Gordon C, Mayer RJ (2005) Ubiquitin and ubiquitin-like proteins as multifunctional signals. Nat Rev Mol Cell Biol 6:599–609. https://doi.org/10.1038/nrm1700CrossRef

Williams RM, Obradovi Z, Mathura V, Braun W, Garner EC, Young J, Takayama S, Brown CJ, Dunker AK (2001) The protein non-folding problem: amino acid determinants of intrinsic order and disorder. Pac. Symp. Biocomput. 89–100. https://doi.org/10.1142/9789814447362_0010

Williamson MP (1994) The structure and function of proline-rich regions in proteins. Biochem J 297:249–260. https://doi.org/10.1042/bj2970249CrossRef

Wißing MH, Brüggemann Y, Steinmann E, Todt D (2021) Virus-Host Cell Interplay during Hepatitis E Virus Infection. Trends Microbiol 29:309–319. https://doi.org/10.1016/j.tim.2020.07.002CrossRef

Wood JP, Silveira JR, Maille NM, Haynes LM, Tracy PB (2011) Prothrombin activation on the activated platelet surface optimizes expression of procoagulant activity. Blood 117:1710–1718. https://doi.org/10.1182/blood-2010-09-311035CrossRef

Wu J, Xiang Z, Zhu C, Yao Y, Bortolanza M, Cao H, Li L (2021) Extrahepatic manifestations related to hepatitis E virus infection and their triggering mechanisms. J Infect 83:298–305. https://doi.org/10.1016/j.jinf.2021.07.021CrossRef

Xing L, Kato K, Li T, Takeda N, Miyamura T, Hammar L, Cheng RH (1999) Recombinant hepatitis E capsid protein self-assembles into a dual-domain T = 1 particle presenting native virus epitopes. Virology 265:35–45. https://doi.org/10.1006/viro.1999.0005CrossRef

Xing L, Li T-C, Mayazaki N, Simon MN, Wall JS, Moore M, Wang C-Y, Takeda N, Wakita T, Miyamura T, Cheng RH (2010) Structure of hepatitis E virion-sized particle reveals an RNA-dependent viral assembly pathway. J Biol Chem 285:33175–33183. https://doi.org/10.1074/jbc.M110.106336CrossRef

Xu M, Behloul N, Wen J, Zhang J, Meng J (2016) Role of asparagine at position 562 in dimerization and immunogenicity of the hepatitis E virus capsid protein. Infect Genet Evol 37:99–107. https://doi.org/10.1016/j.meegid.2015.11.006CrossRef

Yadav KK, Kenney SP (2021) Hepatitis E Virus Immunopathogenesis. Pathog. (Basel, Switzerland) 10. https://doi.org/10.3390/pathogens10091180

Yamashita T, Kaneko S, Shirota Y, Qin W, Nomura T, Kobayashi K, Murakami S (1998) RNA-dependent RNA polymerase activity of the soluble recombinant hepatitis C virus NS5B protein truncated at the C-terminal region. J Biol Chem 273:15479–15486. https://doi.org/10.1074/jbc.273.25.15479CrossRef

Yamashita T, Mori Y, Miyazaki N, Cheng RH, Yoshimura M, Unno H, Shima R, Moriishi K, Tsukihara T, Li TC, Takeda N, Miyamura T, Matsuura Y (2009) Biological and immunological characteristics of hepatitis E virus-like particles based on the crystal structure. Proc. Natl. Acad. Sci. U. S. A. 106, 12986–12991. https://doi.org/10.1073/pnas.0903699106

Yin X, Ambardekar C, Lu Y, Feng Z (2016) Distinct Entry Mechanisms for Nonenveloped and Quasi-Enveloped Hepatitis E Viruses. J Virol 90:4232–4242. https://doi.org/10.1128/jvi.02804-15CrossRef

Yin X, Feng Z (2019) Hepatitis E Virus Entry. https://doi.org/10.3390/v11100883. Viruses 11

Yin X, Ying D, Lhomme S, Tang Z, Walker CM, Xia N, Zheng Z, Feng Z (2018) Origin, antigenicity, and function of a secreted form of ORF2 in hepatitis E virus infection. Proc. Natl. Acad. Sci. U. S. A. 115, 4773–4778. https://doi.org/10.1073/pnas.1721345115

Zaman K, Dudman S, Stene-Johansen K, Qadri F, Yunus M, Sandbu S, Gurley ES, Overbo J, Julin CH, Dembinski JL, Nahar Q, Rahman A, Bhuiyan TR, Rahman M, Haque W, Khan J, Aziz A, Khanam M, Streatfield PK, Clemens JD (2020) HEV study protocol: design of a cluster-randomised, blinded trial to assess the safety, immunogenicity and effectiveness of the hepatitis E vaccine HEV 239 (Hecolin) in women of childbearing age in rural Bangladesh. BMJ Open 10:e033702. https://doi.org/10.1136/bmjopen-2019-033702CrossRef

Zhang J, Liu C-B, Li R-C, Li Y-M, Zheng Y-J, Li Y-P, Luo D, Pan B-B, Nong Y, Ge S-X, Xiong J-H, Shih JW-K, Ng M-H, Xia N-S (2009) Randomized-controlled phase II clinical trial of a bacterially expressed recombinant hepatitis E vaccine. Vaccine 27:1869–1874. https://doi.org/10.1016/j.vaccine.2008.12.061CrossRef

Zhang J, Zhang X-F, Huang S-J, Wu T, Hu Y-M, Wang Z-Z, Wang H, Jiang H-M, Wang Y-J, Yan Q, Guo M, Liu X-H, Li J-X, Yang C-L, Tang Q, Jiang R-J, Pan H-R, Li Y-M, Shih JW-K, Ng M-H, Zhu F-C, Xia N-S (2015) Long-term efficacy of a hepatitis E vaccine. N Engl J Med 372:914–922. https://doi.org/10.1056/NEJMoa1406011CrossRef

Zhang L, Tian Y, Wen Z, Zhang F, Qi Y, Huang W, Zhang H, Wang Y (2016) Asialoglycoprotein receptor facilitates infection of PLC/PRF/5 cells by HEV through interaction with ORF2. J Med Virol 88:2186–2195. https://doi.org/10.1002/jmv.24570CrossRef

Zhang Y, McAtee P, Yarbough PO, Tam AW, Fuerst T (1997) Expression, characterization, and immunoreactivities of a soluble hepatitis E virus putative capsid protein species expressed in insect cells. Clin Diagn Lab Immunol 4:423–428. https://doi.org/10.1128/cdli.4.4.423-428.1997CrossRef

Zhao M, Li X-J, Tang Z-M, Yang F, Wang S-L, Cai W, Zhang K, Xia N-S, Zheng Z-Z (2015) A Comprehensive Study of Neutralizing Antigenic Sites on the Hepatitis E Virus (HEV) Capsid by Constructing, Clustering, and Characterizing a Tool Box. J Biol Chem 290:19910–19922. https://doi.org/10.1074/jbc.M115.649764CrossRef

Zheng Z-Z, Miao J, Zhao M, Tang M, Yeo AET, Yu H, Zhang J, Xia N-S (2010) Role of heat-shock protein 90 in hepatitis E virus capsid trafficking. J Gen Virol 91:1728–1736. https://doi.org/10.1099/vir.0.019323-0CrossRef

Zhou X, Kataoka M, Liu Z, Takeda N, Wakita T, Li T-C (2015) Characterization of self-assembled virus-like particles of dromedary camel hepatitis e virus generated by recombinant baculoviruses. Virus Res 210:8–17. https://doi.org/10.1016/j.virusres.2015.06.022CrossRef

Zhou Y-X, Lee MY-T, Ng JM-H, Chye M-L, Yip W-K, Zee S-Y, Lam E (2006) A truncated hepatitis E virus ORF2 protein expressed in tobacco plastids is immunogenic in mice. World J Gastroenterol 12:306–312. https://doi.org/10.3748/wjg.v12.i2.306CrossRef

Zhou Y, Tzeng W-P, Ye Y, Huang Y, Li S, Chen Y, Frey TK, Yang JJ (2009) A cysteine-rich metal-binding domain from rubella virus non-structural protein is essential for viral protease activity and virus replication. Biochem J 417:477–483. https://doi.org/10.1042/BJ20081468CrossRef

Zhou Y, Tzeng W-P, Yang W, Zhou, Yumei, Ye Y, Lee H, Frey TK, Yang J (2007) Identification of a Ca2+-binding domain in the rubella virus nonstructural protease. J Virol 81:7517–7528. https://doi.org/10.1128/JVI.00605-07CrossRef

Zhu F-C, Zhang J, Zhang X-F, Zhou C, Wang Z-Z, Huang S-J, Wang H, Yang C-L, Jiang H-M, Cai J-P, Wang Y-J, Ai X, Hu Y-M, Tang Q, Yao X, Yan Q, Xian Y-L, Wu T, Li Y-M, Miao J, Ng M-H, Shih JW-K, Xia N-S (2010) Efficacy and safety of a recombinant hepatitis E vaccine in healthy adults: a large-scale, randomised, double-blind placebo-controlled, phase 3 trial. Lancet (London England) 376:895–902. https://doi.org/10.1016/S0140-6736(10)61030-6CrossRef

Titel: Structural aspects of hepatitis E virus
verfasst von: Florencia Cancela
Ofelia Noceti
Juan Arbiza
Santiago Mirazo
Publikationsdatum: 13.09.2022
Verlag: Springer Vienna
Erschienen in: Archives of Virology / Ausgabe 12/2022
Print ISSN: 0304-8608
Elektronische ISSN: 1432-8798
DOI: https://doi.org/10.1007/s00705-022-05575-8

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

Alphablocker schützt vor Miktionsproblemen nach der Biopsie

16.05.2024 alpha-1-Rezeptorantagonisten Nachrichten

Nach einer Prostatabiopsie treten häufig Probleme beim Wasserlassen auf. Ob sich das durch den periinterventionellen Einsatz von Alphablockern verhindern lässt, haben australische Mediziner im Zuge einer Metaanalyse untersucht.

Neue S3-Leitlinie zur unkomplizierten Zystitis: Auf Antibiotika verzichten?

15.05.2024 Harnwegsinfektionen Nachrichten

Welche Antibiotika darf man bei unkomplizierter Zystitis verwenden und wovon sollte man die Finger lassen? Welche pflanzlichen Präparate können helfen? Was taugt der zugelassene Impfstoff? Antworten vom Koordinator der frisch überarbeiteten S3-Leitlinie, Prof. Florian Wagenlehner.

Schadet Ärger den Gefäßen?

14.05.2024 Arteriosklerose Nachrichten

In einer Studie aus New York wirkte sich Ärger kurzfristig deutlich negativ auf die Endothelfunktion gesunder Probanden aus. Möglicherweise hat dies Einfluss auf die kardiovaskuläre Gesundheit.

Intervallfasten zur Regeneration des Herzmuskels?

14.05.2024 Herzinfarkt Nachrichten

Die Nahrungsaufnahme auf wenige Stunden am Tag zu beschränken, hat möglicherweise einen günstigen Einfluss auf die Prognose nach akutem ST-Hebungsinfarkt. Darauf deutet eine Studie an der Uniklinik in Halle an der Saale hin.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 12/2022

Retraction Note to: Upregulation of INF-γ, IL-6, and IL-8 expression during replication of turkey coronavirus in nonepithelial cells obtained from Meleagris gallopavo

Identification of novel totiviruses from the ascomycetous fungus Geotrichum candidum

Acute transcriptomic changes in murine RAW 264.7 cells following pseudorabies virus infection

Long non-coding RNA ENST00000469812 promotes Enterovirus type 71 replication via targeting the miR-4443/NUPR1 axis in rhabdomyosarcoma cells

Complete genome sequence of patchouli chlorosis-associated cytorhabdovirus, a new cytorhabdovirus infecting patchouli plants in Brazil