Download PDF
Semin Liver Dis 2013; 33(01): 003-014
DOI: 10.1055/s-0033-1338110
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Molecular Virology of Hepatitis E Virus

R. Prasida Holla
1   Virology Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India
*   Both authors contributed equally to the article.
,
Imran Ahmad
1   Virology Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India
*   Both authors contributed equally to the article.
,
Zulfazal Ahmad
1   Virology Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India
,
Shahid Jameel
1   Virology Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India
› Author Affiliations
Further Information

Publication History

Publication Date:
05 April 2013 (online)

    Permissions and Reprints

Abstract

Hepatitis E virus (HEV) is the causative agent of hepatitis E. It is a nonenveloped virus with a ∼7.2 kilobases positive-stranded RNA genome. The molecular virology of HEV is getting better understood with the development of replicons and in vitro infection systems, and the discovery of related viruses that infect animal species other than humans. This review focuses on the virology of HEV and updates the current knowledge on the HEV genome and its constituent proteins—ORF1, ORF2, and ORF3, and the viral life cycle.

Keywords

hepatitis E - HEV - ORF1 - ORF2 - ORF3 - RNA replication
 

  • References

  • 1 Emerson SU, Purcell RH. Hepatitis E virus. In: Knipe DM, Howley PM, Griffin DE, Lamb RA, Martin MA, Roizman B, Straus SE, , eds. Fields Virology. 5th ed. Philadelphia: Lippincott Williams & Wilkins; 2006. 3047–3058
    Search in Google Scholar
  • 2 Hepatitis E. Media Centre, World Health Organization. 2012. Available at: http://www.who.int/mediacentre/factsheets/fs280/en/ . Accessed October 15, 2012
    PubMed
  • 3 Khuroo MS. Discovery of hepatitis E: the epidemic non-A, non-B hepatitis 30 years down the memory lane. Virus Res 2011; 161 (1) 3-14
    CrossrefPubMedSearch in Google Scholar
  • 4 Meng XJ, Anderson D, Arankalle VA , et al. Hepeviridae. In: King AMQ, Adams MJ, Carstens EB, Lefkowitz EJ, , eds. Virus Taxonomy, Ninth Report of the International Committee on Taxonomy of Viruses. Oxford: Elsevier/Academic Press; 2011: 1021-1028
    Search in Google Scholar
  • 5 Okamoto H. Genetic variability and evolution of hepatitis E virus. Virus Res 2007; 127 (2) 216-228
    CrossrefPubMedSearch in Google Scholar
  • 6 Uchida T, Suzuki K, Iida F , et al. Animal model, virology and gene cloning of hepatitis E. Gastroenterol Jpn 1991; 26 (Suppl. 03) 148-151
    PubMedSearch in Google Scholar
  • 7 Ticehurst J, Rhodes Jr LL, Krawczynski K , et al. Infection of owl monkeys (Aotus trivirgatus) and cynomolgus monkeys (Macaca fascicularis) with hepatitis E virus from Mexico. J Infect Dis 1992; 165 (5) 835-845
    CrossrefPubMedSearch in Google Scholar
  • 8 McCaustland KA, Krawczynski K, Ebert JW , et al. Hepatitis E virus infection in chimpanzees: a retrospective analysis. Arch Virol 2000; 145 (9) 1909-1918
    CrossrefPubMedSearch in Google Scholar
  • 9 Meng XJ, Halbur PG, Haynes JS , et al. Experimental infection of pigs with the newly identified swine hepatitis E virus (swine HEV), but not with human strains of HEV. Arch Virol 1998; 143 (7) 1405-1415
    CrossrefPubMedSearch in Google Scholar
  • 10 Viswanathan R. Infectious hepatitis in Delhi (1955–56) A critical study: epidemiology. Indian J Med Res 1957; 45 (Suppl. 01) 1-29
    PubMedSearch in Google Scholar
  • 11 Khuroo MS. Discovery of hepatitis E: the epidemic non-A, non-B hepatitis 30 years down the memory lane. Virus Res 2011; 161 (1) 3-14
    CrossrefPubMedSearch in Google Scholar
  • 12 Balayan MS, Andjaparidze AG, Savinskaya SS , et al. Evidence for a virus in non-A, non-B hepatitis transmitted via the fecal-oral route. Intervirology 1983; 20 (1) 23-31
    CrossrefPubMedSearch in Google Scholar
  • 13 Velázquez O, Stetler HC, Avila C , et al. Epidemic transmission of enterically transmitted non-A, non-B hepatitis in Mexico, 1986-1987. JAMA 1990; 263 (24) 3281-3285
    CrossrefPubMedSearch in Google Scholar
  • 14 Zhuang H, Cao XY, Liu CB, Wang GM. Epidemiology of hepatitis E in China. Gastroenterol Jpn 1991; 26 (Suppl. 03) 135-138
    PubMedSearch in Google Scholar
  • 15 Naik SR, Aggarwal R, Salunke PN, Mehrotra NN. A large waterborne viral hepatitis E epidemic in Kanpur, India. Bull World Health Organ 1992; 70 (5) 597-604
    PubMedSearch in Google Scholar
  • 16 Teshale EH, Howard CM, Grytdal SP , et al. Hepatitis E epidemic, Uganda. Emerg Infect Dis 2010; 16 (1) 126-129
    CrossrefPubMedSearch in Google Scholar
  • 17 Nicand E, Armstrong GL, Enouf V , et al. Genetic heterogeneity of hepatitis E virus in Darfur, Sudan, and neighboring Chad. J Med Virol 2005; 77 (4) 519-521
    CrossrefPubMedSearch in Google Scholar
  • 18 Tam AW, Smith MM, Guerra ME , et al. Hepatitis E virus (HEV): molecular cloning and sequencing of the full-length viral genome. Virology 1991; 185 (1) 120-131
    CrossrefPubMedSearch in Google Scholar
  • 19 Reyes GR, Huang CC, Tam AW, Purdy MA. Molecular organization and replication of hepatitis E virus (HEV). Arch Virol Suppl 1993; 7: 15-25
    PubMedSearch in Google Scholar
  • 20 Ahmad I, Holla RP, Jameel S. Molecular virology of hepatitis E virus. Virus Res 2011; 161 (1) 47-58
    CrossrefPubMedSearch in Google Scholar
  • 21 Reyes GR, Purdy MA, Kim JP , et al. Isolation of a cDNA from the virus responsible for enterically transmitted non-A, non-B hepatitis. Science 1990; 247 (4948) 1335-1339
    CrossrefPubMedSearch in Google Scholar
  • 22 Huang CC, Nguyen D, Fernandez J , et al. Molecular cloning and sequencing of the Mexico isolate of hepatitis E virus (HEV). Virology 1992; 191 (2) 550-558
    CrossrefPubMedSearch in Google Scholar
  • 23 Panda SK, Ansari IH, Durgapal H, Agrawal S, Jameel S. The in vitro-synthesized RNA from a cDNA clone of hepatitis E virus is infectious. J Virol 2000; 74 (5) 2430-2437
    CrossrefPubMedSearch in Google Scholar
  • 24 Emerson SU, Zhang M, Meng XJ , et al. Recombinant hepatitis E virus genomes infectious for primates: importance of capping and discovery of a cis-reactive element. Proc Natl Acad Sci U S A 2001; 98 (26) 15270-15275
    CrossrefPubMedSearch in Google Scholar
  • 25 Graff J, Torian U, Nguyen H, Emerson SU. A bicistronic subgenomic mRNA encodes both the ORF2 and ORF3 proteins of hepatitis E virus. J Virol 2006; 80 (12) 5919-5926
    CrossrefPubMedSearch in Google Scholar
  • 26 Huang YW, Opriessnig T, Halbur PG, Meng XJ. 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. J Virol 2007; 81 (6) 3018-3026
    CrossrefPubMedSearch in Google Scholar
  • 27 Ichiyama K, Yamada K, Tanaka T , et al. Determination of the 5′-terminal sequence of subgenomic RNA of hepatitis E virus strains in cultured cells. Arch Virol 2009; 154 (12) 1945-1951
    CrossrefPubMedSearch in Google Scholar
  • 28 Pelosi E, Clarke I. Hepatitis E: a complex and global disease. Emerg Health Threats J 2008; 1: e8
    PubMedSearch in Google Scholar
  • 29 Haqshenas G, Shivaprasad HL, Woolcock PR, Read DH, Meng XJ. Genetic identification and characterization of a novel virus related to human hepatitis E virus from chickens with hepatitis-splenomegaly syndrome in the United States. J Gen Virol 2001; 82 (Pt 10) 2449-2462
    PubMedSearch in Google Scholar
  • 30 Huang FF, Sun ZF, Emerson SU , et al. 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 2004; 85 (Pt 6) 1609-1618
    CrossrefPubMedSearch in Google Scholar
  • 31 Johne R, Heckel G, Plenge-Bönig A , et al. Novel hepatitis E virus genotype in Norway rats, Germany. Emerg Infect Dis 2010; 16 (9) 1452-1455
    CrossrefPubMedSearch in Google Scholar
  • 32 Raj VS, Smits SL, Pas SD , et al. Novel hepatitis E virus in ferrets, the Netherlands. Emerg Infect Dis 2012; 18 (8) 1369-1370
    CrossrefPubMedSearch in Google Scholar
  • 33 Zhao C, Ma Z, Harrison TJ , et al. A novel genotype of hepatitis E virus prevalent among farmed rabbits in China. J Med Virol 2009; 81 (8) 1371-1379
    CrossrefPubMedSearch in Google Scholar
  • 34 Jirintai S , Jinshan, Tanggis, et al. Molecular analysis of hepatitis E virus from farm rabbits in Inner Mongolia, China and its successful propagation in A549 and PLC/PRF/5 cells. Virus Res 2012; 170 (1–2) 126-137
    CrossrefPubMedSearch in Google Scholar
  • 35 Batts W, Yun S, Hedrick R, Winton J. A novel member of the family Hepeviridae from cutthroat trout (Oncorhynchus clarkii). Virus Res 2011; 158 (1–2) 116-123
    CrossrefPubMedSearch in Google Scholar
  • 36 Wang H, Zhang W, Ni B , et al. Recombination analysis reveals a double recombination event in hepatitis E virus. Virol J 2010; 7: 129
    CrossrefPubMedSearch in Google Scholar
  • 37 Kamar N, Izopet J, Cintas P , et al. Hepatitis E virus-induced neurological symptoms in a kidney-transplant patient with chronic hepatitis. Am J Transplant 2010; 10 (5) 1321-1324
    CrossrefPubMedSearch in Google Scholar
  • 38 Lhomme S, Abravanel F, Dubois M , et al. Hepatitis E virus quasispecies and the outcome of acute hepatitis E in solid-organ transplant patients. J Virol 2012; 86 (18) 10006-10014
    CrossrefPubMedSearch in Google Scholar
  • 39 Shukla P, Nguyen HT, Torian U , et al. Cross-species infections of cultured cells by hepatitis E virus and discovery of an infectious virus-host recombinant. Proc Natl Acad Sci U S A 2011; 108 (6) 2438-2443
    CrossrefPubMedSearch in Google Scholar
  • 40 Shukla P, Nguyen HT, Faulk K , et al. 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 2012; 86 (10) 5697-5707
    CrossrefPubMedSearch in Google Scholar
  • 41 Khudyakov YuE, Favorov MO, Jue DL, Hine TK, Fields HA. Immunodominant antigenic regions in a structural protein of the hepatitis E virus. Virology 1994; 198 (1) 390-393
    CrossrefPubMedSearch in Google Scholar
  • 42 Panda SK, Nanda SK, Zafrullah M, Ansari IH, Ozdener MH, Jameel S. An Indian strain of hepatitis E virus (HEV): cloning, sequence, and expression of structural region and antibody responses in sera from individuals from an area of high-level HEV endemicity. J Clin Microbiol 1995; 33 (10) 2653-2659
    PubMedSearch in Google Scholar
  • 43 Koonin EV, Gorbalenya AE, Purdy MA, Rozanov MN, Reyes GR, Bradley DW. 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 1992; 89 (17) 8259-8263
    CrossrefPubMedSearch in Google Scholar
  • 44 Ropp SL, Tam AW, Beames B, Purdy M, Frey TK. Expression of the hepatitis E virus ORF1. Arch Virol 2000; 145 (7) 1321-1337
    CrossrefPubMedSearch in Google Scholar
  • 45 Sehgal D, Thomas S, Chakraborty M, Jameel S. Expression and processing of the hepatitis E virus ORF1 nonstructural polyprotein. Virol J 2006; 3: 38
    CrossrefPubMedSearch in Google Scholar
  • 46 Ansari IH, Nanda SK, Durgapal H , et al. Cloning, sequencing, and expression of the hepatitis E virus (HEV) nonstructural open reading frame 1 (ORF1). J Med Virol 2000; 60 (3) 275-283
    CrossrefPubMedSearch in Google Scholar
  • 47 Ahola T, Kääriäinen L. Reaction in alphavirus mRNA capping: formation of a covalent complex of nonstructural protein nsP1 with 7-methyl-GMP. Proc Natl Acad Sci U S A 1995; 92 (2) 507-511
    CrossrefPubMedSearch in Google Scholar
  • 48 Magden J, Takeda N, Li T , et al. Virus-specific mRNA capping enzyme encoded by hepatitis E virus. J Virol 2001; 75 (14) 6249-6255
    CrossrefPubMedSearch in Google Scholar
  • 49 Karpe YA, Lole KS. RNA 5′-triphosphatase activity of the hepatitis E virus helicase domain. J Virol 2010; 84 (18) 9637-9641
    CrossrefPubMedSearch in Google Scholar
  • 50 Zhang M, Purcell RH, Emerson SU. Identification of the 5′ terminal sequence of the SAR-55 and MEX-14 strains of hepatitis E virus and confirmation that the genome is capped. J Med Virol 2001; 65 (2) 293-295
    CrossrefPubMedSearch in Google Scholar
  • 51 Pichlmair A, Schulz O, Tan CP , et al. RIG-I-mediated antiviral responses to single-stranded RNA bearing 5′-phosphates. Science 2006; 314 (5801) 997-1001
    CrossrefPubMedSearch in Google Scholar
  • 52 Suppiah S, Zhou Y, Frey TK. Lack of processing of the expressed ORF1 gene product of hepatitis E virus. Virol J 2011; 8: 245
    CrossrefPubMedSearch in Google Scholar
  • 53 Karpe YA, Lole KS. Deubiquitination activity associated with hepatitis E virus putative papain-like cysteine protease. J Gen Virol 2011; 92 (Pt 9) 2088-2092
    CrossrefPubMedSearch in Google Scholar
  • 54 Karpe YA, Meng XJ. Hepatitis E virus replication requires an active ubiquitin-proteasome system. J Virol 2012; 86 (10) 5948-5952
    CrossrefPubMedSearch in Google Scholar
  • 55 Karpe YA, Lole KS. NTPase and 5′ to 3′ RNA duplex-unwinding activities of the hepatitis E virus helicase domain. J Virol 2010; 84 (7) 3595-3602
    CrossrefPubMedSearch in Google Scholar
  • 56 Agrawal S, Gupta D, Panda SK. The 3′ end of hepatitis E virus (HEV) genome binds specifically to the viral RNA-dependent RNA polymerase (RdRp). Virology 2001; 282 (1) 87-101
    CrossrefPubMedSearch in Google Scholar
  • 57 Rehman S, Kapur N, Durgapal H, Panda SK. Subcellular localization of hepatitis E virus (HEV) replicase. Virology 2008; 370 (1) 77-92
    CrossrefPubMedSearch in Google Scholar
  • 58 Aguiar RC, Takeyama K, He C, Kreinbrink K, Shipp MA. B-aggressive lymphoma family proteins have unique domains that modulate transcription and exhibit poly(ADP-ribose) polymerase activity. J Biol Chem 2005; 280 (40) 33756-33765
    CrossrefPubMedSearch in Google Scholar
  • 59 Salonen A, Ahola T, Kääriäinen L. Viral RNA replication in association with cellular membranes. Curr Top Microbiol Immunol 2005; 285: 139-173
    PubMedSearch in Google Scholar
  • 60 Snijder EJ, Bredenbeek PJ, Dobbe JC , et al. Unique and conserved features of genome and proteome of SARS-coronavirus, an early split-off from the coronavirus group 2 lineage. J Mol Biol 2003; 331 (5) 991-1004
    CrossrefPubMedSearch in Google Scholar
  • 61 Egloff MP, Malet H, Putics A , et al. Structural and functional basis for ADP-ribose and poly(ADP-ribose) binding by viral macro domains. J Virol 2006; 80 (17) 8493-8502
    CrossrefPubMedSearch in Google Scholar
  • 62 Neuvonen M, Ahola T. Differential activities of cellular and viral macro domain proteins in binding of ADP-ribose metabolites. J Mol Biol 2009; 385 (1) 212-225
    CrossrefPubMedSearch in Google Scholar
  • 63 Purdy MA, Lara J, Khudyakov YE. The hepatitis E virus polyproline region is involved in viral adaptation. PLoS ONE 2012; 7 (4) e35974
    CrossrefPubMedSearch in Google Scholar
  • 64 Purdy MA. Evolution of the hepatitis E virus polyproline region: order from disorder. J Virol 2012; 86 (18) 10186-10193
    CrossrefPubMedSearch in Google Scholar
  • 65 Jameel S, Zafrullah M, Ozdener MH, Panda SK. Expression in animal cells and characterization of the hepatitis E virus structural proteins. J Virol 1996; 70 (1) 207-216
    PubMedSearch in Google Scholar
  • 66 Zafrullah M, Ozdener MH, Kumar R, Panda SK, Jameel S. Mutational analysis of glycosylation, membrane translocation, and cell surface expression of the hepatitis E virus ORF2 protein. J Virol 1999; 73 (5) 4074-4082
    PubMedSearch in Google Scholar
  • 67 Graff J, Zhou YH, Torian U , et al. Mutations within potential glycosylation sites in the capsid protein of hepatitis E virus prevent the formation of infectious virus particles. J Virol 2008; 82 (3) 1185-1194
    CrossrefPubMedSearch in Google Scholar
  • 68 Yamada K, Takahashi M, Hoshino Y , et al. Construction of an infectious cDNA clone of hepatitis E virus strain JE03-1760F that can propagate efficiently in cultured cells. J Gen Virol 2009; 90 (Pt 2) 457-462
    CrossrefPubMedSearch in Google Scholar
  • 69 Jiménez de Oya N, Escribano-Romero E, Blázquez AB , et al. Characterization of hepatitis E virus recombinant ORF2 proteins expressed by vaccinia viruses. J Virol 2012; 86 (15) 7880-7886
    CrossrefPubMedSearch in Google Scholar
  • 70 Li TC, Yamakawa Y, Suzuki K , et al. Expression and self-assembly of empty virus-like particles of hepatitis E virus. J Virol 1997; 71 (10) 7207-7213
    PubMedSearch in Google Scholar
  • 71 Robinson RA, Burgess WH, Emerson SU , et al. Structural characterization of recombinant hepatitis E virus ORF2 proteins in baculovirus-infected insect cells. Protein Expr Purif 1998; 12 (1) 75-84
    CrossrefPubMedSearch in Google Scholar
  • 72 Xing L, Kato K, Li T , et al. Recombinant hepatitis E capsid protein self-assembles into a dual-domain T = 1 particle presenting native virus epitopes. Virology 1999; 265 (1) 35-45
    CrossrefPubMedSearch in Google Scholar
  • 73 Li SW, Zhang J, He ZQ , et al. Mutational analysis of essential interactions involved in the assembly of hepatitis E virus capsid. J Biol Chem 2005; 280 (5) 3400-3406
    PubMedSearch in Google Scholar
  • 74 Yamashita T, Mori Y, Miyazaki N , et al. Biological and immunological characteristics of hepatitis E virus-like particles based on the crystal structure. Proc Natl Acad Sci U S A 2009; 106 (31) 12986-12991
    CrossrefPubMedSearch in Google Scholar
  • 75 Guu TS, Liu Z, Ye Q , et al. Structure of the hepatitis E virus-like particle suggests mechanisms for virus assembly and receptor binding. Proc Natl Acad Sci U S A 2009; 106 (31) 12992-12997
    CrossrefPubMedSearch in Google Scholar
  • 76 Mori Y, Matsuura Y. Structure of hepatitis E viral particle. Virus Res 2011; 161 (1) 59-64
    CrossrefPubMedSearch in Google Scholar
  • 77 Zhang JZ, Ng MH, Xia NS , et al. Conformational antigenic determinants generated by interactions between a bacterially expressed recombinant peptide of the hepatitis E virus structural protein. J Med Virol 2001; 64 (2) 125-132
    CrossrefPubMedSearch in Google Scholar
  • 78 Li SW, Zhang J, Li YM , et al. A bacterially expressed particulate hepatitis E vaccine: antigenicity, immunogenicity and protectivity on primates. Vaccine 2005; 23 (22) 2893-2901
    CrossrefPubMedSearch in Google Scholar
  • 79 Li S, Tang X, Seetharaman J , et al. Dimerization of hepatitis E virus capsid protein E2s domain is essential for virus-host interaction. PLoS Pathog 2009; 5 (8) e1000537
    CrossrefPubMedSearch in Google Scholar
  • 80 Schofield DJ, Glamann J, Emerson SU, Purcell RH. Identification by phage display and characterization of two neutralizing chimpanzee monoclonal antibodies to the hepatitis E virus capsid protein. J Virol 2000; 74 (12) 5548-5555
    CrossrefPubMedSearch in Google Scholar
  • 81 Meng J, Dai X, Chang JC , et al. Identification and characterization of the neutralization epitope(s) of the hepatitis E virus. Virology 2001; 288 (2) 203-211
    CrossrefPubMedSearch in Google Scholar
  • 82 Zhou YH, Purcell RH, Emerson SU. An ELISA for putative neutralizing antibodies to hepatitis E virus detects antibodies to genotypes 1, 2, 3, and 4. Vaccine 2004; 22 (20) 2578-2585
    CrossrefPubMedSearch in Google Scholar
  • 83 Shrestha MP, Scott RM, Joshi DM , et al. Safety and efficacy of a recombinant hepatitis E vaccine. N Engl J Med 2007; 356 (9) 895-903
    CrossrefPubMedSearch in Google Scholar
  • 84 Zhu FC, Zhang J, Zhang XF , et al. Efficacy and safety of a recombinant hepatitis E vaccine in healthy adults: a large-scale, randomised, double-blind placebo-controlled, phase 3 trial. Lancet 2010; 376 (9744) 895-902
    CrossrefPubMedSearch in Google Scholar
  • 85 Xing L, Wang JC, Li TC , et al. Spatial configuration of hepatitis E virus antigenic domain. J Virol 2011; 85 (2) 1117-1124
    CrossrefPubMedSearch in Google Scholar
  • 86 Li TC, Suzaki Y, Ami Y, Dhole TN, Miyamura T, Takeda N. Protection of cynomolgus monkeys against HEV infection by oral administration of recombinant hepatitis E virus-like particles. Vaccine 2004; 22 (3-4) 370-377
    CrossrefPubMedSearch in Google Scholar
  • 87 Sanford BJ, Opriessnig T, Kenney SP, Dryman BA, Córdoba L, Meng XJ. Assessment of the cross-protective capability of recombinant capsid proteins derived from pig, rat, and avian hepatitis E viruses (HEV) against challenge with a genotype 3 HEV in pigs. Vaccine 2012; 30 (44) 6249-6255
    PubMedSearch in Google Scholar
  • 88 He S, Miao J, Zheng Z , et al. Putative receptor-binding sites of hepatitis E virus. J Gen Virol 2008; 89 (Pt 1) 245-249
    CrossrefPubMedSearch in Google Scholar
  • 89 Zheng ZZ, Miao J, Zhao M , et al. Role of heat-shock protein 90 in hepatitis E virus capsid trafficking. J Gen Virol 2010; 91 (Pt 7) 1728-1736
    CrossrefPubMedSearch in Google Scholar
  • 90 Kalia M, Chandra V, Rahman SA, Sehgal D, Jameel S. Heparan sulfate proteoglycans are required for cellular binding of the hepatitis E virus ORF2 capsid protein and for viral infection. J Virol 2009; 83 (24) 12714-12724
    CrossrefPubMedSearch in Google Scholar
  • 91 Kalia M, Jameel S. Virus entry paradigms. Amino Acids 2011; 41 (5) 1147-1157
    CrossrefPubMedSearch in Google Scholar
  • 92 Surjit M, Jameel S, Lal SK. Cytoplasmic localization of the ORF2 protein of hepatitis E virus is dependent on its ability to undergo retrotranslocation from the endoplasmic reticulum. J Virol 2007; 81 (7) 3339-3345
    CrossrefPubMedSearch in Google Scholar
  • 93 John L, Thomas S, Herchenröder O, Pützer BM, Schaefer S. Hepatitis E virus ORF2 protein activates the pro-apoptotic gene CHOP and anti-apoptotic heat shock proteins. PLoS ONE 2011; 6 (9) e25378
    CrossrefPubMedSearch in Google Scholar
  • 94 Surjit M, Varshney B, Lal SK. 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 2012; 13 (1) 7
    CrossrefPubMedSearch in Google Scholar
  • 95 Emerson SU, Nguyen H, Torian U, Purcell RH. ORF3 protein of hepatitis E virus is not required for replication, virion assembly, or infection of hepatoma cells in vitro. J Virol 2006; 80 (21) 10457-10464
    CrossrefPubMedSearch in Google Scholar
  • 96 Graff J, Nguyen H, Yu C , et al. 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 2005; 79 (11) 6680-6689
    CrossrefPubMedSearch in Google Scholar
  • 97 Zafrullah M, Ozdener MH, Panda SK, Jameel S. The ORF3 protein of hepatitis E virus is a phosphoprotein that associates with the cytoskeleton. J Virol 1997; 71 (12) 9045-9053
    PubMedSearch in Google Scholar
  • 98 Chandra V, Kar-Roy A, Kumari S, Mayor S, Jameel S. The hepatitis E virus ORF3 protein modulates epidermal growth factor receptor trafficking, STAT3 translocation, and the acute-phase response. J Virol 2008; 82 (14) 7100-7110
    CrossrefPubMedSearch in Google Scholar
  • 99 Kannan H, Fan S, Patel D, Bossis I, Zhang YJ. The hepatitis E virus open reading frame 3 product interacts with microtubules and interferes with their dynamics. J Virol 2009; 83 (13) 6375-6382
    CrossrefPubMedSearch in Google Scholar
  • 100 Kar-Roy A, Korkaya H, Oberoi R, Lal SK, Jameel S. The hepatitis E virus open reading frame 3 protein activates ERK through binding and inhibition of the MAPK phosphatase. J Biol Chem 2004; 279 (27) 28345-28357
    CrossrefPubMedSearch in Google Scholar
  • 101 Korkaya H, Jameel S, Gupta D , et al. The ORF3 protein of hepatitis E virus binds to Src homology 3 domains and activates MAPK. J Biol Chem 2001; 276 (45) 42389-42400
    CrossrefPubMedSearch in Google Scholar
  • 102 Moin SM, Panteva M, Jameel S. The hepatitis E virus Orf3 protein protects cells from mitochondrial depolarization and death. J Biol Chem 2007; 282 (29) 21124-21133
    CrossrefPubMedSearch in Google Scholar
  • 103 Chandra V, Kalia M, Hajela K, Jameel S. The ORF3 protein of hepatitis E virus delays degradation of activated growth factor receptors by interacting with CIN85 and blocking formation of the Cbl-CIN85 complex. J Virol 2010; 84 (8) 3857-3867
    CrossrefPubMedSearch in Google Scholar
  • 104 Taneja S, Sen S, Gupta VK, Aggarwal R, Jameel S. Plasma and urine biomarkers in acute viral hepatitis E. Proteome Sci 2009; 7: 39
    CrossrefPubMedSearch in Google Scholar
  • 105 Tyagi S, Surjit M, Roy AK, Jameel S, Lal SK. The ORF3 protein of hepatitis E virus interacts with liver-specific alpha1-microglobulin and its precursor alpha1-microglobulin/bikunin precursor (AMBP) and expedites their export from the hepatocyte. J Biol Chem 2004; 279 (28) 29308-29319
    CrossrefPubMedSearch in Google Scholar
  • 106 Tyagi S, Surjit M, Lal SK. The 41-amino-acid C-terminal region of the hepatitis E virus ORF3 protein interacts with bikunin, a kunitz-type serine protease inhibitor. J Virol 2005; 79 (18) 12081-12087
    CrossrefPubMedSearch in Google Scholar
  • 107 Ratra R, Kar-Roy A, Lal SK. The ORF3 protein of hepatitis E virus interacts with hemopexin by means of its 26 amino acid N-terminal hydrophobic domain II. Biochemistry 2008; 47 (7) 1957-1969
    CrossrefPubMedSearch in Google Scholar
  • 108 Ratra R, Kar-Roy A, Lal SK. 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 2009; 90 (Pt 6) 1359-1370
    CrossrefPubMedSearch in Google Scholar
  • 109 Surjit M, Oberoi R, Kumar R, Lal SK. Enhanced alpha1 microglobulin secretion from hepatitis E virus ORF3-expressing human hepatoma cells is mediated by the tumor susceptibility gene 101. J Biol Chem 2006; 281 (12) 8135-8142
    CrossrefPubMedSearch in Google Scholar
  • 110 Moin SM, Chandra V, Arya R, Jameel S. The hepatitis E virus ORF3 protein stabilizes HIF-1alpha and enhances HIF-1-mediated transcriptional activity through p300/CBP. Cell Microbiol 2009; 11 (9) 1409-1421
    CrossrefPubMedSearch in Google Scholar
  • 111 Chandra V, Holla P, Ghosh D, Chakrabarti D, Padigaru M, Jameel S. The hepatitis E virus ORF3 protein regulates the expression of liver-specific genes by modulating localization of hepatocyte nuclear factor 4. PLoS ONE 2011; 6 (7) e22412
    CrossrefPubMedSearch in Google Scholar
  • 112 Takahashi M, Yamada K, Hoshino Y , et al. 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 2008; 153 (9) 1703-1713
    CrossrefPubMedSearch in Google Scholar
  • 113 Emerson SU, Nguyen HT, Torian U, Burke D, Engle R, Purcell RH. 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. J Virol 2010; 84 (18) 9059-9069
    CrossrefPubMedSearch in Google Scholar
  • 114 Nagashima S, Takahashi M , Jirintai, et al. A PSAP motif in the ORF3 protein of hepatitis E virus is necessary for virion release from infected cells. J Gen Virol 2011; 92 (Pt 2) 269-278
    CrossrefPubMedSearch in Google Scholar
  • 115 Nagashima S, Takahashi M, Jirintai S , et al. Tumour susceptibility gene 101 and the vacuolar protein sorting pathway are required for the release of hepatitis E virions. J Gen Virol 2011; 92 (Pt 12): 2838-2848
    CrossrefPubMedSearch in Google Scholar
  • 116 Kenney SP, Pudupakam RS, Huang YW, Pierson FW, LeRoith T, Meng XJ. The PSAP motif within the ORF3 protein of an avian strain of the hepatitis E virus is not critical for viral infectivity in vivo but plays a role in virus release. J Virol 2012; 86 (10) 5637-5646
    CrossrefPubMedSearch in Google Scholar
  • 117 Chen BJ, Lamb RA. Mechanisms for enveloped virus budding: can some viruses do without an ESCRT?. Virology 2008; 372 (2) 221-232
    CrossrefPubMedSearch in Google Scholar
  • 118 Reyes GR, Huang CC, Tam AW, Purdy MA. Molecular organization and replication of hepatitis E virus (HEV). Arch Virol Suppl 1993; 7: 15-25
    PubMedSearch in Google Scholar
  • 119 Kapur N, Thakral D, Durgapal H, Panda SK. Hepatitis E virus enters liver cells through receptor-dependent clathrin-mediated endocytosis. J Viral Hepat 2012; 19 (6) 436-448
    CrossrefPubMedSearch in Google Scholar
  • 120 Nanda SK, Panda SK, Durgapal H, Jameel S. Detection of the negative strand of hepatitis E virus RNA in the livers of experimentally infected rhesus monkeys: evidence for viral replication. J Med Virol 1994; 42 (3) 237-240
    CrossrefPubMedSearch in Google Scholar
  • 121 Williams TP, Kasorndorkbua C, Halbur PG , et al. Evidence of extrahepatic sites of replication of the hepatitis E virus in a swine model. J Clin Microbiol 2001; 39 (9) 3040-3046
    CrossrefPubMedSearch in Google Scholar
  • 122 Ippagunta SK, Naik S, Jameel S, Ramana KN, Aggarwal R. Viral RNA but no evidence of replication can be detected in the peripheral blood mononuclear cells of hepatitis E virus-infected patients. J Viral Hepat 2011; 18 (9) 668-672
    CrossrefPubMedSearch in Google Scholar
  • 123 Sriram B, Thakral D, Panda SK. Targeted cleavage of hepatitis E virus 3′ end RNA mediated by hammerhead ribozymes inhibits viral RNA replication. Virology 2003; 312 (2) 350-358
    CrossrefPubMedSearch in Google Scholar
  • 124 Huang F, Zhou J, Yang Z , et al. RNA interference inhibits hepatitis E virus mRNA accumulation and protein synthesis in vitro. Vet Microbiol 2010; 142 (3-4) 261-267
    CrossrefPubMedSearch in Google Scholar
  • 125 Kamar N, Rostaing L, Abravanel F , et al. Ribavirin therapy inhibits viral replication on patients with chronic hepatitis e virus infection. Gastroenterology 2010; 139 (5) 1612-1618
    CrossrefPubMedSearch in Google Scholar
  • 126 de Niet A, Zaaijer HL, ten Berge I, Weegink CJ, Reesink HW, Beuers U. Chronic hepatitis E after solid organ transplantation. Neth J Med 2012; 70 (6) 261-266
    PubMedSearch in Google Scholar
  • 127 Pischke S, Stiefel P, Franz B , et al. Chronic hepatitis e in heart transplant recipients. Am J Transplant 2012; 12 (11) 3128-3133
    CrossrefPubMedSearch in Google Scholar
  • 128 Gerolami R, Borentain P, Raissouni F, Motte A, Solas C, Colson P. Treatment of severe acute hepatitis E by ribavirin. J Clin Virol 2011; 52 (1) 60-62
    CrossrefPubMedSearch in Google Scholar
  • 129 Goyal R, Kumar A, Panda SK, Paul SB, Acharya SK. Ribavirin therapy for hepatitis E virus-induced acute on chronic liver failure: a preliminary report. Antivir Ther 2012; 17 (6) 1091-1096
    CrossrefPubMedSearch in Google Scholar