Abstract
Hepatitis E virus (HEV) is an enterically transmitted (other routes of transmission may exist) RNA virus that causes an acute, self-limiting hepatitis in immunecompetent subjects, but may also cause chronic infection in immunesuppressed subjects. Infection with HEV may be asymptomatic or may cause hepatitis varying in degree of severity from mild to fulminant disease. Fulminant hepatitis E has been reported with increased frequency in pregnant women.
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Khuroo MS. Study of an epidemic of non-A, non-B hepatitis. Possibility of another human hepatitis virus distinct from post-transfusion non-A, non-B type. J Med. 1980;68:818–24.
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;20:23–31.
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;247:1335–9.
Chandra V, Taneja S, Kalia M, Jameel S. Molecular biology and pathogenesis of hepatitis E virus. J Biosci. 2008;33:451–64.
Bradley DW, Andjaparidze AG, Cook Jr EH, et al. Etiologic agent of enterically-transmitted non-A, non-B hepatitis. J Gen Virol. 1988;69:731–8.
Emerson SU, Arankalle VA, Purcell RH. Thermal Stability of Hepatitis E Virus. J Infect Dis. 2005;192:930–3.
He S et al. Putative receptor-binding sites of hepatitis E virus. J Gen Virol. 2008;89:245–9.
Li TC et al. Essential elements of the capsid protein for self-assembly into empty virus-like particles of hepatitis E virus. J Virol. 2005;79:12999–3006.
Xing L et al. Recombinant hepatitis E capsid protein self-assembles into a dual-domain T = 1 particle presenting native virus epitopes. Virology. 1999;265:35–45.
Guu TS, Liu Z, Ye Q, Mata DA, Li K, Yin C, 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;106:12992–7.
Wang Y, Zhang H, Ling R, Li H, Harrison TJ. The complete sequence of hepatitis E virus genotype 4 reveals an alternative strategy for translation of open reading frames 2 and 3. J Gen Virol. 2000;81:1675–86.
Sarin SK, Kumar M. Hepatitis E. In: Boyer T, Manns M, Wright TL, editors. Zakim Boyer’s hepatology: a textbook of liver disease. 5th ed. Philadelphia: Saunders; 2007. p. 693–724.
Ropp SL, Tam AW, Beames B, Purdy M, Frey TK. Expression of the hepatitis E virus ORF1. Arch Virol. 2000;145:1321–37.
Sehgal D, Thomas S, Chakraborty M, Jameel S. Expression and processing of the hepatitis E virus ORF1 nonstructural polyprotein. Virol J. 2006;3:38.
Emerson SU, Zhang M, Meng XJ, Nguyen H, St Claire M, Govindarajan S, 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;98:15270–5.
Magden J, Takeda N, Li T, Auvinen P, Ahola T, Miyamura T, et al. Virus-specific mRNA capping enzyme encoded by hepatitis E virus. J Virol. 2001;75:6249–55.
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;81:3339–45.
Graff J, Zhou YH, Torian U, Nguyen H, St Claire M, Yu C, 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;82:1185–94.
Surjit M, Jameel S, Lal SK. The ORF2 protein of hepatitis E virus binds the 5′ region of viral RNA. J Virol. 2004;78:320–8.
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;80:5919–26.
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;80:10457–64.
Graff J, Nguyen H, Yu C, Elkins WR, St Claire M, Purcell RH, 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;79:6680–9.
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;279:28345–57.
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;47:1957–69.
Korkaya H, Jameel S, Gupta D, Tyagi S, Kumar R, Zafrullah M, et al. The ORF3 protein of hepatitis E virus binds to Src homology 3 domains and activates MAPK. J Biol Chem. 2001;276:42389–400.
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):1359–70.
Moin SM, Panteva M, Jameel S. The hepatitis E virus Orf3 protein protects cells from mitochondrial depolarization and death. J Biol Chem. 2007;282:21124–33.
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):6375–82.
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;79:12081–7.
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;281:8135–42.
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;11:1409–21.
Yamada K, Takahashi M, Hoshino Y, Takahashi H, Ichiyama K, Nagashima S, et al. ORF3 protein of hepatitis E virus is essential for virion release from infected cells. J Gen Virol. 2009;90(Pt 8):1880–91.
He S, Miao J, Zheng Z, Wu T, Xie M, Tang M, et al. Putative receptor-binding sites of hepatitis E virus. J Gen Virol. 2008;89:245–9.
Rehman S, Kapur N, Durgapal H, Panda SK. Subcellular localization of hepatitis E virus (HEV) replicase. Virology. 2008;370(1):77–92.
Emerson SU, Nguyen H, Graff J, Stephany DA, Brockington A, Purcell RH. In vitro replication of hepatitis E virus (HEV) genomes and of an HEV replicon expressing green fluorescent protein. J Virol. 2004;78:4838–46.
Hagedorn CH. Phylogenetic analysis of global hepatitis E virus sequences: genetic diversity, subtypes and zoonosis. Rev Med Virol. 2006;16:5–36.
Tam AW, Smith MM, Guerra ME, Huang CC, Bradley DW, Fry KE, et al. Hepatitis E virus (HEV): molecular cloning and sequencing of the full-length viral genome. Virology. 1991;185:120–31.
Huang CC, Nguyen D, Fernandez J, Yun KY, Fry KE, Bradley DW, et al. Molecular cloning and sequencing of the Mexico isolate of hepatitis E virus (HEV). Virology. 1992;191:550–8.
Kwo PY, Schlauder GG, Carpenter HA, Murphy PJ, Rosenblatt JE, Dawson GJ, et al. Acute hepatitis E by a new isolate acquired in the United States. Mayo Clin Proc. 1997;72:1133–6.
Okamoto H. Genetic variability and evolution of hepatitis E virus. Virus Res. 2007;127(2):216–28.
Wang Y, Ling R, Erker JC, Zhang H, Li H, Desai S, et al. A divergent genotype of hepatitis E virus in Chinese patients with acute hepatitis. J Gen Virol. 1999;80:169–77.
Takahashi K, Toyota J, Karino Y, Kang JH, Maekubo H, Abe N, et al. Estimation of the mutation rate of hepatitis E virus based on a set of closely related 7.5-year-apart isolates from Sapporo, Japan. Hepatology. 2004;29:212–5.
Grandadam M, Tebbal S, Caron M, Siriwardana M, Larouze B, Koeck JL, et al. Evidence for hepatitis E virus quasispecies. J Gen Virol. 2004;85:3189–94.
Purcell RH, Emerson SU. Hepatitis E virus. In: Knipe DM, Howley PM, Griffin DE, Lamb RA, Martin MA, Roizman B, Straus SE, editors. Fields virology. 4th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2001. p. 3051–61.
Shrestha SM, Shrestha S, Tsuda F, Nishizawa T, Takahashi M, Gotanda Y, et al. Genetic changes in hepatitis E virus of subtype 1a in patients with sporadic acute hepatitis E in Kathmandu, Nepal, from 1997 to 2002. J Gen Virol. 2004;85:97–104.
Ticehurst J, Rhodes LL, Jr KK, Asher LV, Engler WF, Mensing TL, et al. Infection of owl monkeys (Aotus trivirgatus) and cynomolgus monkeys (Macaca fascicularis) with hepatitis E virus from Mexico. J Infect Dis. 1992;165:835–45.
McCaustland KA, Krawczynski K, Ebert JW, Balayan MS, Andjaparidze AG, Spelbring JE, et al. Hepatitis E virus infection in chimpanzees: a retrospective analysis. Arch Virol. 2000;145:1909–18.
Williams TP, Kasorndorkbua C, Halbur PG, Haqshenas G, Guenette DK, Toth TE, et al. Evidence of extrahepatic sites of replication of the hepatitis E virus in a swine model. J Clin Microbiol. 2001;39:3040–6.
Li W, Sun Q, She R, Wang D, Duan X, Yin J, et al. Experimental infection of Mongolian gerbils by a genotype 4 strain of swine hepatitis E virus. J Med Virol. 2009;81(9):1591–6.
Huang F, Zhang W, Gong G, Yuan C, Yan Y, Yang S, et al. Experimental infection of Balb/c nude mice with hepatitis E virus. BMC Infect Dis. 2009;9:93.
Wei S, Walsh P, Huang R, To SS. 93G, a novel sporadic strain of hepatitis E virus in South China isolated by cell culture. J Med Virol. 2000;61:311–8.
Kazachkov Yu A, Balayan MS, Ivannikova TA, Panina LI, Orlova TM, Zamyatina NA, et al. Hepatitis E virus in cultivated cells. Arch Virol. 1992;127:399–402.
Meng J, Dubreuil P, Pillot J. A new PCR-based seroneutralization assay in cell culture for diagnosis of hepatitis E. J Clin Microbiol. 1997;35:1373–7.
Tanaka T, Takahashi M, Kusano E, Okamoto H. Development and evaluation of an efficient cell-culture system for Hepatitis E virus. J Gen Virol. 2007;88:903–11.
Takahashi M, Tanaka T, Azuma M, Kusano E, Aikawa T, Shibayama T, et al. Prolonged fecal shedding of hepatitis E virus (HEV) during sporadic acute hepatitis E: evaluation of infectivity of HEV in fecal specimens in a cell culture system. J Clin Microbiol. 2007;45:3671–9.
Prinja S, Kumar S, Reddy GM, Ratho RK, Kumar R. Investigation of viral hepatitis E outbreak in a town in Haryana. J Commun Dis. 2008;40(4):249–54.
Clayson ET, Vaughn DW, Innis BL, Shrestha MP, Pandey R, Malla DB. Association of hepatitis E virus with an outbreak of hepatitis at a military training camp in Nepal. J Med Virol. 1998;54:178–82.
Rab MA, Bile MK, Mubarik MM, et al. Water-borne hepatitis E virus epidemic in Islamabad, Pakistan: a common source outbreak traced to the malfunction of a modern water treatment plant. Am J Trop Med Hyg. 1997;57:151–7.
Sedyaningsih-Mamahit ER, Larasati RP, Laras K, et al. First documented outbreak of hepatitis E virus transmission in Java, Indonesia. Trans R Soc Trop Med Hyg. 2002;96:398–404.
Isaacson M, Frean J, He J, Seriwatana J, Innis BL. An outbreak of hepatitis E in Northern Namibia, 1983. Am J Trop Med Hyg. 2000;62:619–25.
Velazquez O, Stetler HC, Avila C, et al. Epidemic transmission of enterically transmitted non-A, non-B hepatitis in Mexico, 1986–1987. JAMA. 1990;263:3281–5.
Zhuang H, Cao XY, Liu CB, Wang GM. Epidemiology of hepatitis E in China. Gastroenterol Jpn. 1991;26 suppl 3:135–8.
Skidmore SJ. Factors in spread of hepatitis E. Lancet. 1999;354:1049–50.
Chadha MS, Walimbe AM, Chobe LP, Arankalle VA. Comparison of etiology of sporadic acute and fulminant viral hepatitis in hospitalized patients in Pune, India during 1978–81 and 1994–97. Indian J Gastroenterol. 2003;22:11–5.
Arankalle VA, Tsarev SA, Chadha MS, et al. Age-specific prevalence of antibodies to hepatitis A and E viruses in Pune, India, 1982 and 1992. J Infect Dis. 1995;171:447–50.
Tran HT, Ushijima H, Quang VX, et al. Prevalence of hepatitis virus types B through E and genotypic distribution of HBV and HCV in Ho Chi Minh City, Vietnam. Hepatol Res. 2003;26:275–80.
Naik SR, Aggarwal R, Salunke PN, et al. A large waterborne viral hepatitis E epidemic in Kanpur, India. Bull World Health Organ. 1992;70:597–604.
Mushahwar IK, Dawson GJ, Bile KM, et al. Serological studies of an enterically transmitted non-A, non-B hepatitis in Somalia. J Med Virol. 1993;40:218–21.
Aggarwal R, Shahi H, Naik S, et al. Evidence in favour of high infection rate with hepatitis E virus among young children in India. J Hepatol. 1997;26:1425–30.
Vishwanathan R. Infectious hepatitis in Delhi (1955–1956): a critical study: epidemiology. Indian J Med Res. 1957;45(suppl):1–29.
Khoroo MS, Deurmeyer W, Zargar SA, et al. Acute sporadic non-A, non-B, hepatitis in India. Am J Epidemiol. 1983;118:360–4.
Dalton HR, Bendall R, Ijaz S. Hepatitis E: an emerging infection in developed countries. Lancet Infect Dis. 2008;8(11):698–709.
Kuniholm MH, Purcell RH, McQuillan GM, Engle RE, Wasley A, Nelson KE. Epidemiology of hepatitis E virus in the United States: results from the Third National Health and Nutrition Examination Survey, 1988–1994. J Infect Dis. 2009;200(1):48–56.
Stoszek SK, Engle RE, Abdel-Hamid M, et al. Hepatitis E antibody seroconversion without disease in highly endemic rural Egyptian communities. Trans R Soc Trop Med Hyg. 2006;100:89–94.
Shata MT, Barrett A, Shire NJ, et al. Characterization of hepatitis E specific cell-mediated immune response using IFN-gamma ELISPOT assay. J Immunol Methods. 2007;328:152–61.
De Silva AN, Muddu AK, Iredale JP, Sheron N, Khakoo SI, Pelosi E. Unexpectedly high incidence of indigenous acute hepatitis E within south Hampshire: time for routine testing? J Med Virol. 2008;80:283–8.
Corwin AL, Tien NT, Bounlu K, et al. The unique riverine ecology of hepatitis E virus transmission in South-East Asia. Trans R Soc Trop Med Hyg. 1999;93:255–60.
Somani SK, Aggarwal R, Naik SR, et al. A serological study of intrafamilial spread from patients with sporadic hepatitis E virus infection. J Viral Hepat. 2003;10:446–9.
Robson SC, Adams S, Brink N, et al. Hospital outbreak of hepatitis E. Lancet. 1992;339:1424–5.
Tsarev SA, Tsarev TS, Emerson SU, et al. Experimental hepatitis E in pregnant rhesus monkeys: failure to transmit hepatitis E virus (HEV) to offspring and evidence of naturally acquired antibodies to HEV. J Infect Dis. 1995;172:31–7.
Khuroo MS, Kamili S, Jameel S. Vertical transmission of hepatitis E virus. Lancet. 1995;345:1025–6.
Singh S, Mohanty A, Joshi YK, et al. Mother-to-child transmission of hepatitis E virus infection. Indian J Pediatr. 2003;70:37–9.
Kumar RM, Uduman S, Rana S, et al. Sero-prevalence and mother-to-infant transmission of hepatitis E virus among pregnant women in the United Arab Emirates. Eur J Obstet Gynecol Reprod Biol. 2001;100:9–15.
Tschopp A, Joller H, Jeggli S, Widmeier S, Steffen R, Hilfiker S, et al. Hepatitis E, Helicobacter pylori and peptic ulcers in workers exposed to sewage: a prospective cohort study. Occup Environ Med. 2009;66(1):45–50.
Casares PC, Pina S, Buti M, et al. Hepatitis E virus epidemiology in industrialized countries. Emerg Infect Dis. 2003;9:448–54.
Vaidya SR, Tilekar BN, Walimbe AM, Arankalle VA. Increased risk of hepatitis E in sewage workers from India. J Occup Environ Med. 2003;45:1167–70.
Ceylan A, Ertem M, Ilcin E, Ozekinci T. A special risk group for hepatitis E infection: Turkish agricultural workers who use untreated waste water for irrigation. Epidemiol Infect. 2003;131:753–6.
Ng KP, He J, Saw TL, Lyles CM. A seroprevalence study of viral hepatitis E infection in human immunodeficiency virus type 1 infected subjects in Malaysia. Med J Malaysia. 2000;55(1):58–64.
Madejón A, Vispo E, Bottecchia M, Sánchez-Carrillo M, García-Samaniego J, Soriano V. Lack of hepatitis E virus infection in HIV patients with advanced immunodeficiency or idiopathic liver enzyme elevations. J Viral Hepat. 2009;16:895–6.
Mansuy JM, Legrand-Abravanel F, Calot JP, Peron JM, Alric L, Agudo S, et al. High prevalence of anti-hepatitis E virus antibodies in blood donors from South West France. J Med Virol. 2008;80(2):289–93.
Mansuy JM, Huynh A, Abravanel F, Recher C, Peron JM, Izopet J. Molecular evidence of patient-to-patient transmission of hepatitis E virus in a hematology ward. Clin Infect Dis. 2009;48(3):373–4.
Matsubayashi K, Kang JH, Sakata H, Takahashi K, Shindo M, Kato M, et al. A case of transfusion-transmitted hepatitis E caused by blood from a donor infected with hepatitis E virus via zoonotic food-borne route. Transfusion. 2008;48(7):1368–75.
Fukada S, Sunaga J, Saito N, Fujimura K, Itoh Y, Sasaki M, et al. Prevalence of antibodies to hepatitis E virus among Japanese blood donors: identification of three blood donors infected with a genotype 3 hepatitis E virus. J Med Virol. 2004;73:554–61.
Yunoki M, Yamamoto S, Tanaka H, Nishigaki H, Tanaka Y, Nishida A, et al. Extent of hepatitis E virus elimination is affected by stabilizers present in plasma products and pore size of nanofilters. Vox Sang. 2008;95(2):94–100.
Toyoda H, Honda T, Hayashi K, Katano Y, Goto H, Kumada T, et al. Prevalence of hepatitis E virus IgG antibody in Japanese patients with hemophilia. Intervirology. 2008;51(1):21–5.
Nubling M, Hofmann F, Tiller FW. Occupational risk for hepatitis A and hepatitis E among health care professionals? Infection. 2002;30:94–7.
Mitsui T, Tsukamoto Y, Hirose A, Suzuki S, Yamazaki C, Masuko K, et al. Distinct changing profiles of hepatitis A and E virus infection among patients with acute hepatitis, patients on maintenance hemodialysis and healthy individuals in Japan. J Med Virol. 2006;78(8):1015–24.
Taremi M, Khoshbaten M, Gachkar L, EhsaniArdakani M, Zali M. Hepatitis E virus infection in hemodialysis patients: a seroepidemiological survey in Iran. BMC Infect Dis. 2005;5(1):36.
Lee CC, Shih YL, Laio CS, Lin SM, Huang MM, Chen CJ, et al. Prevalence of antibody to hepatitis E virus among haemodialysis patients in Taiwan: possible infection by blood transfusion. Nephron Clin Pract. 2005;99(4):c122–7.
Meng XJ. Hepatitis E virus: animal reservoirs and zoonotic risk. Vet Microbiol. 2010;27:256–65.
Caron M, Enouf V, Than SC, Dellamonica L, Buisson Y, Nicand E. Identification of genotype 1 hepatitis E virus in samples from swine in Cambodia. J Clin Microbiol. 2006;44:3440–2.
Halbur PG, Kasorndorkbua C, Gilbert C, et al. Comparative pathogenesis of infection of pigs with hepatitis E viruses recovered from a pig and a human. J Clin Microbiol. 2001;39:918–23.
Chobe LP, Lole KS, Arankalle VA. Full genome sequence and analysis of Indian swine hepatitis E virus isolate of genotype 4. Vet Microbiol. 2006;114:240–51.
Meng XJ, Purcell RH, Halbur PG, et al. A novel virus in swine is closely related to the human hepatitis E virus. Proc Natl Acad Sci U S A. 1997;94:9860–5.
Schlauder GG, Dawson GJ, Erker JC, et al. The sequence and phylogenetic analysis of a novel hepatitis E virus isolated from a patient with acute hepatitis reported in the United States. J Gen Virol. 1998;79:447–56.
Arankalle VA, Chobe LP, Joshi MV, Chadha MS, Kundu B, Walimbe AM. Human and swine hepatitis E viruses from western India belong to different genotypes. J Hepatol. 2002;36:417–25.
Banks M, Heath GS, Grierson SS, et al. Evidence for the presence of hepatitis E virus in pigs in the United Kingdom. Vet Rec. 2004;154:223–7.
Galiana C, Fernández-Barredo S, García A, Gómez MT, Pérez-Gracia MT. Occupational exposure to hepatitis E virus (HEV) in swine workers. Am J Trop Med Hyg. 2008;78(6):1012–5.
Bouwknegt M, Engel B, Herremans MM, et al. Bayesian estimation of hepatitis E virus seroprevalence for populations with different exposure levels to swine in the Netherlands. Epidemiol Infect. 2008;136:567–76.
Kase JA, Correa MT, Sobsey MD. Detection and molecular characterization of swine hepatitis E virus in North Carolina swine herds and their faecal wastes. J Water Health. 2009;7(2):344–57.
Kasorndorkbua C, Opriessnig T, Huang FF, et al. Infectious swine hepatitis E virus is present in pig manure storage facilities on United States farms, but evidence of water contamination is lacking. Appl Environ Microbiol. 2005;71:7831–7.
Matsuda H, Okada K, Takahashi K, Mishiro S. Severe hepatitis E virus infection after ingestion of uncooked liver from a wild boar. J Infect Dis. 2003;188:944.
Tei S, Kitajima N, Takahashi K, Mishiro S. Zoonotic transmission of hepatitis E virus from deer to human beings. Lancet. 2003;362:371–3.
Bouwknegt M, Lodder-Verschoor F, van der Poel WH, Rutjes SA, Roda Husman AM. Hepatitis E virus RNA in commercial porcine livers in the Netherlands. J Food Prot. 2007;70:2889–95.
Feagins AR, Opriessnig T, Guenette DK, Halbur PG, Meng XJ. Inactivation of infectious hepatitis E virus present in commercial pig livers sold in local grocery stores in the United States. Int J Food Microbiol. 2008;123:32–7.
Dalton HR, Bendall RP, Pritchard C. Pig meat consumption and mortality from chronic liver disease. Gut. 2008;57 suppl 1:A76.
Feagins AR, Opriessnig T, Guenette DK, Halbur PG, Meng XJ. Detection and characterization of infectious hepatitis E virus from commercial pig livers sold in local grocery stores in the USA. J Gen Virol. 2007;88:912–7.
Arankalle VA, Chadha MS, Banerjee K, et al. Hepatitis E virus infection in pregnant rhesus monkeys. Indian J Med Res. 1993;97:4–8.
Bradley DW, Krawczynski K, Cook EH, et al. Enterically transmitted non-A, non-B hepatitis: etiology of disease and laboratory studies in non human primates. In: Zukermann AJ, editor. Viral hepatitis and liver disease. New York: Alan R. Liss; 1988. p. 138–47.
Chauhan A, Jameel S, Dilawari JB, et al. Hepatitis E virus transmission to a volunteer. Lancet. 1993;341:149–50.
Nanda SK, Ansari JH, Acharya SK, et al. Protracted viremia during acute sporadic hepatitis E virus infection. Gastroenterology. 1995;108:225–30.
Tsarev SA, Tsareva TS, Emerson SU, et al. Infectivity titration of a prototype strain of hepatitis E virus in cynomolgus monkeys. J Med Virol. 1994;43:135–42.
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;165:835–45.
Soe S, Uchida T, Suzuki K, et al. Enterically transmitted non-A, non-B hepatitis in cynomolgus monkeys: morphology and probable mechanism of hepatocellular necrosis. Liver. 1989;9:135–45.
Tsarev SA, Tsareva TS, Emerson SU, et al. Recombinant vaccine against hepatitis E: dose response and protection against heterologous challenge. Vaccine. 1997;15:1834–8.
Purcell RH, Ticehurst JR. Enterically transmitted non-A, non-B hepatitis: epidemiology and clinical characteristics. In: Zuckerman AJ, editor. Viral hepatitis and liver disease. New York: Allan R Liss Press; 1997. p. 131–7.
Pal R, Aggarwal R, Naik SR, Das V, Das S, Naik S. Immunological alterations in pregnant women with acute hepatitis E. J Gastroenterol Hepatol. 2005;20:1094–101.
Patra S, Kumar A, Trivedi SS, Puri M, Sarin SK. Maternal and fetal outcomes in pregnant women with acute hepatitis E virus infection. Ann Intern Med. 2007;147:28–33.
Jilani N, Das BC, Husain SA, Baweja UK, Chattopadhya D, Gupta RK, et al. Hepatitis E virus infection and fulminant hepatic failure during pregnancy. J Gastroenterol Hepatol. 2007;22:676–82.
Prusty BK, Hedau S, Singh A, Kar P, Das BC. Selective suppression of NF-κ(kappa)Bp65 in hepatitis virus-infected pregnant women manifesting severe liver damage and high mortality. Mol Med. 2007;13:518–26.
Favorov MO, Khudyakov YE, Mast EE, et al. IgM and IgG antibodies to hepatitis E virus (HEV) detected by an enzyme immunoassay based on an HEV-specific artificial recombinant mosaic protein. J Med Virol. 1996;50:50–8.
Khuroo MS, Kamili S, Dar MY, et al. Hepatitis E and long-term antibody status. Lancet. 1993;341:1355.
Zhang S, Tian D, Zhang Z, Xiong J, Yuan Q, Ge S, et al. Clinical significance of anti-HEV IgA in diagnosis of acute genotype 4 hepatitis E virus infection negative for anti-HEV IgM. Dig Dis Sci. 2009;54:2512–8.
Wu T, Zhang J, Su ZJ, Liu JJ, Wu XL, Wu XL, et al. Specific cellular immune response in hepatitis E patients. Intervirology. 2008;51(5):322–7.
Srivastava R, Aggarwal R, Bhagat MR, Chowdhury A, Naik S. Alterations in natural killer cells and natural killer T cells during acute viral hepatitis E. J Viral Hepat. 2008;15(12):910–6.
Mast E, Krawczynski K. Hepatitis E: an overview. Ann Rev Med. 1996;47:257.
Peron JM, Danjoux M, Kamar N, et al. Liver histology in patients with sporadic acute hepatitis E: a study of 11 patients from southwest France. Virchows Arch. 2007;450:405–10.
Malcolm P, Dalton H, Hussaini HS, Mathew J. The histology of acute autochthonous hepatitis E virus infection. Histopathology. 2007;51:190–4.
Lockwood GL, Fernandez-Barredo S, Bendall R, Banks M, Ijaz S, Dalton HR. Hepatitis E autochthonous infection in chronic liver disease. Eur J Gastroenterol Hepatol. 2008;20:800–3.
Haagsma EB, van den Berg AP, Porte RJ, et al. Chronic hepatitis E virus infection in liver transplant recipients. Liver Transpl. 2008;14:547–53.
Kamar N, Selves J, Mansuy JM, et al. Hepatitis E virus and chronic hepatitis in organ-transplant recipients. N Engl J Med. 2008;358:811–7.
Gupta DN, Smetana HF. The histopathology of viral hepatitis as seen in the Delhi epidemic (1955–56). Indian J Med Res. 1957;45(suppl):101–13.
Khuroo MS, Saleem M, Teli MR, et al. Failure to detect chronic liver disease after epidemic non-A, non-B hepatitis. Lancet. 1980;2:97–8.
Tamura A, Shimizu YK, Tanaka T, Kuroda K, Arakawa Y, Takahashi K, et al. Persistent infection of hepatitis E virus transmitted by blood transfusion in a patient with T-cell lymphoma. Hepatol Res. 2007;37(2):113–20.
Schildgen O, Müller A, Simon A. Chronic hepatitis E and organ transplants. N Engl J Med. 2008;358:2521–2.
Ollier L, Tieulie N, Sanderson F, Heudier P, Giordanengo V, Fuzibet JG, et al. Chronic hepatitis after hepatitis E virus infection in a patient with non-Hodgkin lymphoma taking rituximab. Ann Intern Med. 2009;150(6):430–1.
Aggarwal R. Hepatitis E: does it cause chronic hepatitis? Hepatology. 2008;48(4):1328–30.
Balayan MS. HEV infection: historical perspectives, global epidemiology, and clinical features. In: Hollinger FB, Lemon SM, Margolis H, editors. Viral hepatitis and liver disease. Baltimore: Williams & Wilkins; 1991. p. 498–501.
Sanyal MC. Infectious hepatitis in Delhi (1955–56): a critical study. Observations in armed forces personnel. Indian J Med Res. 1957;45(suppl):91–9.
Kumar Acharya S, Kumar Sharma P, Singh R, et al. Hepatitis E virus (HEV) infection in patients with cirrhosis is associated with rapid decompensation and death. J Hepatol. 2007;46:387–94.
Kumar M, Sharma BC, Sarin SK. Hepatitis E virus as an etiology of acute exacerbation of previously unrecognized asymptomatic patients with hepatitis B virus-related chronic liver disease. J Gastroenterol Hepatol. 2008;23:883–7.
Radha Krishna Y, Saraswat VA, Das K, Himanshu G, Yachha SK, Aggarwal R, et al. Clinical features and predictors of outcome in acute hepatitis A and hepatitis E virus hepatitis on cirrhosis. Liver Int. 2009;29(3):392–8.
Khuroo MS, Kamili S. Aetiology, clinical course and outcome of sporadic acute viral hepatitis in pregnancy. J Viral Hepat. 2003;10:61–9.
Khuroo MS, Khuroo M. Association of severity of HEV infection in the mother and vertically transmitted infection in fetus [letter to Editor, rapid response]. Ann Intern Med. 2007;147:33.
Poddar U, Thapa BR, Prasad A, Singh K. Changing spectrum of sporadic acute viral hepatitis in Indian children. J Trop Pediatr. 2002;48:210–3.
Kumar A, Yachha SK, Poddar U, Singh U, Aggarwal R. Does co-infection with multiple viruses adversely influence the course and outcome of sporadic acute viral hepatitis in children? J Gastroenterol Hepatol. 2006;21(10):1533–7.
Zaki Mel S, Salama OS, Mansour FA, Hossein S. Hepatitis E virus coinfection with hepatotropic viruses in Egyptian children. J Microbiol Immunol Infect. 2008;41(3):254–8.
Dixit VK, Abhilash VB, Kate MP, Jain AK. Hepatitis E infection with Bell’s palsy. J Assoc Physicians India. 2006;54:418.
Thapa R, Mallick D, Ghosh A. Childhood hepatitis E infection complicated by acute immune thrombocytopenia. J Pediatr Hematol Oncol. 2009;31(2):151.
Dalton HR, Stableforth W, Thurairajah P, et al. Autochthonous hepatitis E in southwest England: natural history, complications and seasonal variation, and hepatitis E virus IgG seroprevalence in blood donors, the elderly and patients with chronic liver disease. Eur J Gastroenterol Hepatol. 2008;20:784–90.
Dalton HR, Hazeldine S, Banks M, Ijaz S, Bendall R. Locally acquired hepatitis E in chronic liver disease. Lancet. 2007;369:1260.
Peron JM, Bureau C, Poirson H, et al. Fulminant liver failure from acute autochthonous hepatitis E in France: description of seven patients with acute hepatitis E and encephalopathy. J Viral Hepat. 2007;14:298–303.
Dalton HR, Fellows HJ, Stableforth W, et al. The role of hepatitis E virus testing in drug-induced liver injury. Aliment Pharmacol Ther. 2007;26:1429–35.
Mizuo H, Yazaki Y, Sugawara K, Tsuda F, Takahashi M, Nishizawa T, et al. Possible risk factors for the transmission of hepatitis E virus and for the severe form of hepatitis E acquired locally in Hokkaido. Japan J Med Virol. 2005;76:341–9.
Takahashi M, Nishizawa T, Yoshikawa A, Sato S, Isoda N, Ido K, et al. Identification of two distinct genotypes of hepatitis E virus in a Japanese patient with acute hepatitis who had not travelled abroad. J Gen Virol. 2002;83:1931–40.
Arankalle VA, Sreenivasan MA, Popper H, et al. Aetiological association of a virus-like particle with enterically transmitted non-A, non-B hepatitis. Lancet. 1988;1:550–4.
Jothikumar N, Cromeans TL, Robertson BH, Meng XJ, Hill VR. A broadly reactive one-step real-time RT-PCR assay for rapid and sensitive detection of hepatitis E virus. J Virol Methods. 2006;131:65–71.
Gyarmati P, Mohammed N, Norder H, et al. Universal detection of hepatitis E virus by two real-time PCR assays: TaqMan and primer-probe energy transfer. J Virol Methods. 2007;146:226–35.
Zhao C, Li L, Harrison TJ, Wang Q, Song A, Fan J, et al. Relationships among viral diagnostic markers and markers of liver function in acute hepatitis E. J Gastroenterol. 2009;44(2):139–45.
Chen HY, Lu Y, Howard T, et al. Comparison of a new immunochromatographic test to enzyme-linked immunosorbent assay for rapid detection of immunoglobulin M antibodies to hepatitis E virus in human sera. Clin Diagn Lab Immunol. 2005;12:593–8.
Lin CC, Wu JC, Chang TT, et al. Diagnostic value of immunoglobulin G (IgG) and IgM anti-hepatitis E virus (HEV) tests based on HEV RNA in an area where hepatitis E is not endemic. J Clin Microbiol. 2000;38:3915–8.
Takahashi M, Kusakai S, Mizuo H, et al. Simultaneous detection of immunoglobulin A (IgA) and IgM antibodies against hepatitis E virus (HEV) is highly specific for diagnosis of acute HEV infection. J Clin Microbiol. 2005;43:49–56.
Zhang JZ, Im SW, Lau SH, et al. Occurrence of hepatitis E virus IgM, low avidity IgG serum antibodies, and viremia in sporadic cases of non-A, -B, and -C acute hepatitis. J Med Virol. 2002;66:40–8.
Bendall R, Ellis V, Ijaz S, Thurairajah P, Dalton HR. Serological response to hepatitis E virus genotype 3 infection: IgG quantitation, avidity, and IgM response. J Med Virol. 2008;80:95–101.
Li RC, Ge SX, Li YP, et al. Seroprevalence of hepatitis E virus infection, rural southern People’s Republic of China. Emerg Infect Dis. 2006;12:1682–8.
Yu C, Engle RE, Bryan JP, Emerson SU, Purcell RH. Detection of immunoglobulin M antibodies to hepatitis E virus by class capture enzyme immunoassay. Clin Diagn Lab Immunol. 2003;10:579–86.
Innis BL, Seriwatana J, Robinson RA, et al. Quantitation of immunoglobulin to hepatitis E virus by enzyme immunoassay. Clin Diagn Lab Immunol. 2002;9:639–48.
Ferguson M, Walker D, Mast E, Fields H. Report of a collaborative study to assess the suitability of a reference reagent for antibodies to hepatitis E virus. Biologicals. 2002;30:43–8.
Herremans M, Bakker J, Duizer E, Vennema H. Koopmans MP.Use of serological assays for diagnosis of hepatitis E virus genotype 1 and 3 infections in a setting of low endemicity. Clin Vaccine Immunol. 2007;14:562–8.
Tsarev SA, Tsareva TS, Emerson SU, et al. Successful passive and active immunization of cynomolgus monkeys against hepatitis E. Proc Natl Acad Sci U S A. 1994;91:10198–202.
Khuroo MS, Dar MY, Hepatitis E. Evidence for person-to-person transmission and inability of low dose immune serum globulin from an Indian source to prevent it. Indian J Gastroenterol. 1992;11:113–6.
He J, Kuschner RA, Dewar V, Voet P, Asher LV, Vaughn DW. Characterization of monoclonal antibodies to hepatitis E virus (HEV) capsid protein and identification of binding activity. J Biomed Sci. 2007;14(5):555–63.
Wang L, Zhuang H. Hepatitis E: an overview and recent advances in vaccine research. World J Gastroenterol. 2004;10:2157–62.
Zhang M, Emerson SU, Nguyen H, Engle RE, Govindarajan S, Gerin JL, et al. Immunogenicity and protective efficacy of a vaccine prepared from 53 kDa truncated hepatitis E virus capsid protein expressed in insect cells. Vaccine. 2001;20:853–7.
Safary A. Perspectives of vaccination against hepatitis E. Intervirology. 2001;44:162–6.
Shrestha MP, Scott RM, Joshi DM, Mammen Jr MP, Thapa GB, Thapa N, et al. Safety and efficacy of a recombinant hepatitis E vaccine. N Engl J Med. 2007;356:895–903.
Arankalle VA, Lole KS, Deshmukh TM, Srivastava S, Shaligram US. Challenge studies in Rhesus monkeys immunized with candidate hepatitis E vaccines: DNA, DNA-prime-protein-boost and DNA-protein encapsulated in liposomes. Vaccine. 2009;27(7):1032–9.
Purcell RH, Nguyen H, Shapiro M, Engle RE, Govindarajan S, Blackwelder WC, et al. Pre-clinical immunogenicity and efficacy trial of a recombinant hepatitis E vaccine. Vaccine. 2003;21:2607–15.
Krawczynski K. Hepatitis E vaccine – ready for prime time? N Engl J Med. 2007;356:949–51.
Tacke F, Trautwein C. Efficient recombinant hepatitis E virus vaccine: mission accomplished? Hepatology. 2007;46(3):941–3.
Li SW, Zhang J, Li YM, Ou SH, Huang GY, He ZQ, et al. A bacterially expressed particulate hepatitis E vaccine: antigenicity, immunogenicity and protectivity on primates. Vaccine. 2005;23:2893–901.
Zhang JZ, Ng MH, Xia NS, Lau SH, Che XY, Chau TN, 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;64:125–32.
Li SW, Zhang J, He ZQ, Gu Y, Liu RS, Lin J, et al. Mutational analysis of essential interactions involved in the assembly of hepatitis E virus capsid. J Biol Chem. 2005;280:3400–6.
Zhang J, Gu Y, Ge SX, Li SW, He ZQ, Huang GY, et al. Analysis of hepatitis E virus neutralization sites using monoclonal antibodies directed against a virus capsid protein. Vaccine. 2005;23:2881–92.
Wu T, Wu XL, Ou SH, Lin CX, Cheng T, Li SW, et al. Difference of T cell and B cell activation in two homologous proteins with similar antigenicity but great distinct immunogenicity. Mol Immunol. 2007;44:3261–6.
Ge S, Zhang J, Huang G, Pang S, Zhou K, Xia N. The immuno-protect study of a hepatitis E virus ORF2 peptide expressed in E. coli. Wei Sheng Wu Xue Bao. 2003;43:35–42.
Zhang J, Liu CB, Li RC, Li YM, Zheng YJ, Li YP, et al. Randomized-controlled phase II clinical trial of a bacterially expressed recombinant hepatitis E vaccine. Vaccine. 2009;27(12):1869–74.
Rose SR, Keystone JS. Hepatitis. In: International Travel Health Guide: 2007 Online Edition. At <www.travmed.com/health_guide/ch12.htm>. Accessed 12 Jan 2010.
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Sarin, S.K., Kumar, M. (2011). Viral Hepatitis E. In: Monga, S. (eds) Molecular Pathology of Liver Diseases. Molecular Pathology Library, vol 5. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-7107-4_40
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