Chapter 88 : Hepatitis A and E Viruses

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:
Zoom in

Hepatitis A and E Viruses , Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555816728/9781555814632_Chap88-1.gif /docserver/preview/fulltext/10.1128/9781555816728/9781555814632_Chap88-2.gif


The hepatitis A virus (HAV) and hepatitis E virus (HEV ) are enterically transmitted, and both cause acute and generally self-limiting infections without significant long-term carrier status. Acute infections with any of the hepatitis viruses cannot be distinguished on clinical characteristics or pathological examinations, and the diseases caused by HAV and HEV are considered together. Clinical presentation of acute viral hepatitis commonly begins with nonspecific, "flu-like" symptoms such as fever, headache, anorexia, nausea, and abdominal discomfort. The high proportion of window period cases found in this study contrasts with the high sensitivity of HAV IgM detection in other studies and may be related to high-dose infections with short incubation periods, and/ or early case detection due to active surveillance of the outbreak. The authors also reported the detection of HAV RNA in 26% of patients initially classified as having acute, sporadic non-A, non-C hepatitis. The detection of HEV-specific IgM should therefore become the method of choice for diagnosis of acute HEV infection in areas of low prevalence. Early assays for HEV-specific IgM showed false-positive reactivity in 3% of U.S. blood donors, roughly equivalent to the rate of IgG reactivity, which limited their usefulness in areas where HEV is nonendemic.

Citation: Anderson D, Counihan N. 2011. Hepatitis A and E Viruses , p 1423-1436. In Versalovic J, Carroll K, Funke G, Jorgensen J, Landry M, Warnock D (ed), Manual of Clinical Microbiology, 10th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816728.ch88

Key Concept Ranking

Hepatitis E virus
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


Image of FIGURE 1

Genome replication and proteins of HAV and HEV. Both viruses have positivestrand RNA genomes of around 7,200 to 7,500 nt. (A) HAV replication proceeds via transcription from the genome to give full-length negative-strand RNA and then positive-strand RNA, which can either be assembled into the virus particle or used to translate further copies of a single, giant polyprotein which is processed by viral protease to yield the replicative proteins and capsid proteins. Assembly of five copies of each of the three capsid proteins (VP0, VP3, and PX) into pentamers and then 12 pentamers into capsids is required to form the antigenic sites of the virus. (B) Details of HEV replication are unknown, but it most likely produces a full-length negative-strand RNA and then full-length positive-strand RNA (new viral genomes) as well as subgenomic mRNAs which are used to translate the ORF2 (capsid) and ORF3 proteins, as well as the ORF1 polyprotein, which is cleaved at unknown sites to yield the replicative proteins. Cleavage of full-length PORF2 results in assembly of virus-like particles from the truncated product, but the size of the authentic viral capsid protein is unknown. Modified from reference , with permission.

Citation: Anderson D, Counihan N. 2011. Hepatitis A and E Viruses , p 1423-1436. In Versalovic J, Carroll K, Funke G, Jorgensen J, Landry M, Warnock D (ed), Manual of Clinical Microbiology, 10th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816728.ch88
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 2

Export of HAV from hepatocytes. Polarized hepatocytes are organized in complex structures within the liver, with bile canaliculi representing grooves formed from the apical domains of adjacent hepatocytes (inset). Bile is secreted into the canaliculi via the apical membranes and then flows into the small intestine via a network of ducts. The basolateral surfaces of hepatocytes are in contact with the hepatic blood supply and underlying tissue. Following replication in hepatocytes, HAV is exported via basolateral membranes towards the blood supply (step 1, arrow). The virus is then transported back through the cell (step 2, arrow), possibly by transcytosis, to the apical surface and secreted into bile canaliculi.

Citation: Anderson D, Counihan N. 2011. Hepatitis A and E Viruses , p 1423-1436. In Versalovic J, Carroll K, Funke G, Jorgensen J, Landry M, Warnock D (ed), Manual of Clinical Microbiology, 10th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816728.ch88
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 3

Serologic and virologic courses of infection with HAV or HEV. For HAV, the serologic responses shown are typical of those detected with numerous commercially available assays. For HEV, the serologic responses shown are those that probably occur in most patients, but the detection of these responses will vary widely depending on the assays used. High levels of HAV-specific IgG provide lifelong protection from reinfection, but HEV-specific IgG declines rapidly during the first 6 months and might not persist at protective levels for life. Modified from reference with permission.

Citation: Anderson D, Counihan N. 2011. Hepatitis A and E Viruses , p 1423-1436. In Versalovic J, Carroll K, Funke G, Jorgensen J, Landry M, Warnock D (ed), Manual of Clinical Microbiology, 10th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816728.ch88
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 4

RPOC tests for HEV-specific IgM. Undiluted serum (25 μl) was added to the specimen window (a) and allowed to migrate through part of the membrane. Approximately 30 s later, 3 drops of buffer were added to the buffer window (b), the separator was removed by pulling the protruding end (c), and 1 drop of wash buffer was added to the specimen window. Results were visible through the viewing window (d) after 8 min. Samples are considered positive for IgM anti-HEV if two colored lines appear in the viewing window, and negative for IgM anti-HEV if a colored line appears only at the control line. Test kits are as described previously ( ), kindly provided by MP Biomedicals. Data are from our laboratory.

Citation: Anderson D, Counihan N. 2011. Hepatitis A and E Viruses , p 1423-1436. In Versalovic J, Carroll K, Funke G, Jorgensen J, Landry M, Warnock D (ed), Manual of Clinical Microbiology, 10th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816728.ch88
Permissions and Reprints Request Permissions
Download as Powerpoint


1. Adcock, W. L.,, A. MacGregor,, J. R. Davies,, M. Hattarki,, D. A. Anderson,, and N. H. Goss. 1998. Chromatographic removal and heat inactivation of hepatitis A virus during manufacture of human albumin. Biotechnol. Appl. Biochem. 28:8594.
2. Aggarwal, R.,, S. Kamili,, J. Spelbring,, and K. Krawczynski. 2001. Experimental studies on subclinical hepatitis E virus infection in cynomolgus macaques. J. Infect. Dis. 184:13801385.
2a. Anderson, D.,, M. Riddell,, F. Li,, I. Shrestha,, T. Howard,, G. Perry,, and G. Mearns. 2000. Abstr. 10th Int. Symp. Viral Hepatitis Liver Dis., abstr. E001.
3. Anderson, D. A. 1987. Cytopathology, plaque assay, and heat inactivation of hepatitis A virus strain HM175. J. Med. Virol. 22:3544.
4. Anderson, D. A., 2000. Waterborne hepatitis, p. 295305. In S. C. Specter,, R. L. Hodinka,, and S. A. Young (ed.), Clinical Virology Manual, 3rd ed. ASM Press, Washington, DC.
5. Anderson, D. A.,, F. Li,, M. A. Riddell,, T. Howard,, H.-F. Seow,, J. Torresi,, G. Perry,, D. Sumarsidi,, S. M. Shrestha,, and I. L. Shrestha. 1999. ELISA for IgG-class antibody to hepatitis E virus based on a highly conserved, conformational epitope expressed in Escherichia coli. J. Virol. Methods 81:131142.
6. Anderson, D. A.,, and B. C. Ross. 1990. Morphogenesis of hepatitis A virus: isolation and characterization of subviral particles. J. Virol. 64:52845289.
7. Anderson, D. A.,, and I. L. Shrestha,. 2002. Hepatitis E virus, p. 10611074. In D. D. Richman,, R. J. Whitley,, and F. G. Hayden (ed.), Clinical Virology. ASM Press, Washington, DC.
8. Angell, S. Y.,, and R. H. Behrens. 2005. Risk assessment and disease prevention in travelers visiting friends and relatives. Infect. Dis. Clin. N. Am. 19:4965.
9. Arankalle, V. A.,, M. S. Chadha,, S. A. Tsarev,, S. U. Emerson,, A. R. Risbud,, K. Banerjee,, and R. H. Purcell. 1994. Seroepidemiology of water-borne hepatitis in India and evidence for a third enterically-transmitted hepatitis agent. Proc. Natl. Acad. Sci. USA 91:34283432.
10. Arankalle, V. A.,, and L. P. Chobe. 2000. Retrospective analysis of blood transfusion recipients: evidence for posttransfusion hepatitis E. Vox Sang. 79:7274.
11. Aydogdu, S.,, F. Ozgenc,, S. Yurtsever,, S. A. Akman,, Y. Tokat,, and R. V. Yagci. 2003. Our experience with fulminant hepatic failure in Turkish children: etiology and outcome. J. Trop. Pediatr. 49:367370.
12. Balayan, M. S. 1997. Epidemiology of hepatitis E virus infection. J. Viral Hepat. 4:155165.
13. Bell, B. P., 2002. Global epidemiology of hepatitis A: implications for control strategies, p. 359365. In H. S. Margolis,, M. J. Alter,, and T. J. Liang (ed.), Viral Hepatitis and Liver Disease. International Medical Press, London, United Kingdom.
14. Bell, B. P.,, D. A. Anderson,, and S. M. Feinstone,. 2005. Hepatitis A virus, p. 21622185. In G. L. Mandell,, J. E. Bennett,, and R. Dolin (ed.), Principles and Practice of Infectious Diseases, 6th ed. Elsevier, Philadelphia, PA.
15. Blank, C. A.,, D. A. Anderson,, M. Beard,, and S. M. Lemon. 2000. Infection of polarized cultures of human intestinal epithelial cells with hepatitis A virus: vectorial release of progeny virions through apical cellular membranes. J. Virol. 74:64766484.
16. Bradley, D.,, A. Andjaparidze,, E. H. Cook, Jr.,, K. McCaustland,, M. Balayan,, H. Stetler,, O. Velazquez,, B. Robertson,, C. Humphrey,, M. Kane,, and I. Weisfuse. 1988. Aetiological agent of enterically transmitted non-A, non-B hepatitis. J. Gen. Virol. 69:731738.
17. Buisson, Y.,, M. Grandadam,, E. Nicand,, P. Cheval,, H. van Cuyck-Gandre,, B. Innis,, P. Rehel,, P. Coursaget,, R. Teyssou,, and S. Tsarev. 2000. Identification of a novel hepatitis E virus in Nigeria. J. Gen. Virol. 81:903909.
18.Centers for Disease Control and Prevention. 2005. Positive test results for acute hepatitis A virus infection among persons with no recent history of acute hepatitis—United States, 2002-2004. MMWR Morb. Mortal. Wkly. Rep. 54:453456.
19. Chen, H. Y.,, Y. Lu,, T. Howard,, D. Anderson,, P. Y. Fong,, W. P. Hu,, C. P. Chia,, and M. Guan. 2005. 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. 12:593598.
20. Chen, Y.,, J. Mao,, Y. Hong,, L. Yang,, Z. Ling,, and W. Yu. 2001. Genetic analysis of wild-type hepatitis A virus strains. Chin. Med. J. (Engl.) 114:422423.
21. Clayson, E. T.,, K. S. Myint,, R. Snitbhan,, D. W. Vaughn,, B. L. Innis,, L. Chan,, P. Cheung,, and M. P. Shrestha. 1995. Viremia, fecal shedding, and IgM and IgG responses in patients with hepatitis E. J. Infect. Dis. 172:927933..
22. Clayson, E. T.,, M. P. Shrestha,, D. W. Vaughn,, R. Snitbhan,, K. B. Shrestha,, C. F. Longer,, and B. L. Innis. 1997. Rates of hepatitis E virus infection and disease among adolescents and adults in Kathmandu, Nepal. J. Infect. Dis. 176:763766.
23. Conaty, S.,, P. Bird,, G. Bell,, E. Kraa,, G. Grohmann,, and J. M. McAnulty. 2000. Hepatitis A in New South Wales, Australia from consumption of oysters: the first reported outbreak. Epidemiol. Infect. 124:121130.
24. Corwin, A.,, K. Jarot,, I. Lubis,, K. Nasution,, S. Suparmawo,, A. Sumardiati,, S. Widodo,, S. Nazir,, G. Orndorff,, Y. Choi,, R. Tan,, A. Sie,, S. Wignall,, R. Graham,, and K. Hyams. 1995. Two years’ investigation of epidemic hepatitis E virus transmission in West Kalimantan (Borneo), Indonesia. Trans. R. Soc. Trop. Med. Hyg. 89:262265.
25. Daniels, D.,, S. Grytdal,, and A. Wasley. 2009. Surveillance for acute viral hepatitis—United States, 2007. MMWR Morb. Mortal. Wkly. Rep. 58:127.
26. Darwish, M. A.,, R. Faris,, J. D. Clemens,, M. R. Rao,, and R. Edelman. 1996. High seroprevalence of hepatitis A, B, C, and E viruses in residents in an Egyptian village in the Nile Delta: a pilot study. Am. J. Trop. Med. Hyg. 54:554558.
27. Dawson, G. J.,, K. H. Chau,, C. M. Cabal,, P. O. Yarbough,, G. R. Reyes,, and I. K. Mushahwar. 1992. Solid-phase enzyme-linked immunosorbent assay for hepatitis E virus IgG and IgM antibodies utilizing recombinant antigens and synthetic peptides. J. Virol. Methods 38:175186.
28. Dawson, G. J.,, I. K. Mushahwar,, K. H. Chau,, and G. L. Gitnick. 1992. Detection of long-lasting antibody to hepatitis E virus in a US traveller to Pakistan. Lancet 340:426427.
29. de Paula, V. S.,, L. M. Villar,, L. M. Morais,, L. L. Lewis- Ximenez,, C. Niel,, and A. M. Gaspar. 2004. Detection of hepatitis A virus RNA in serum during the window period of infection. J. Clin. Virol. 29:254259.
30. Desenclos, J. C.,, K. C. Klontz,, M. H. Wilder,, O. V. Nainan,, H. S. Margolis,, and R. A. Gunn. 1991. A multistate outbreak of hepatitis A caused by the consumption of raw oysters. Am. J. Public Health 81:12681272.
31. Emerson, S. U.,, V. A. Arankalle,, and R. H. Purcell. 2005. Thermal stability of hepatitis E virus. J. Infect. Dis. 192:930933.
32. Emerson, S. U.,, P. Clemente-Casares,, N. Moiduddin,, V. A. Arankalle,, U. Torian,, and R. H. Purcell. 2006. Putative neutralization epitopes and broad cross-genotype neutralization of hepatitis E virus confirmed by a quantitative cellculture assay. J. Gen. Virol. 87:697704.
33. Emerson, S. U.,, H. Nguyen,, J. Graff,, D. A. Stephany,, A. Brockington,, and R. H. Purcell. 2004. In vitro replication of hepatitis E virus (HEV) genomes and of an HEV replicon expressing green fluorescent protein. J. Virol. 78:48384846.
34. Emerson, S. U.,, H. Nguyen,, U. Torian,, and R. H. Purcell. 2006. ORF3 protein of hepatitis E virus is not required for replication, virion assembly, or infection of hepatoma cells in vitro. J. Virol. 80:1045710464.
35. Emerson, S. U.,, S. A. Tsarev,, and R. H. Purcell. 1991. Biological and molecular comparisons of human (HM-175) and simian (AGM-27) hepatitis A viruses. J. Hepatol. 13(Suppl. 4):S144S145.
36. Emerson, S. U.,, M. Zhang,, X. J. Meng,, H. Nguyen,, M. St. Claire,, S. Govindarajan,, Y. K. Huang,, and R. H. Purcell. 2001. Recombinant hepatitis E virus genomes infectious for primates: importance of capping and discovery of a cis-reactive element. Proc. Natl. Acad. Sci. USA 98:1527015275.
37. Fainboim, L.,, M. C. Canero Velasco,, C. Y. Marcos,, M. Ciocca,, A. Roy,, G. Theiler,, M. Capucchio,, S. Nuncifora,, L. Sala,, and M. Zelazko. 2001. Protracted, but not acute, hepatitis A virus infection is strongly associated with HLADRB* 1301, a marker for pediatric autoimmune hepatitis. Hepatology 33:15121517.
38. Fauquet, C. M.,, M. A. Mayo,, J. Maniloff,, U. Desselberger,, and L. A. Ball (ed.). 2005. Virus Taxonomy. Eighth Report of the International Committee on Taxonomy of Viruses. Elsevier Academic Press, San Diego, CA.
39. Favorov, M. O.,, Y. E. Khudyakov,, E. E. Mast,, T. L. Yashina,, C. N. Shapiro,, N. S. Khudyakova,, D. L. Jue,, G. G. Onischenko,, H. S. Margolis,, and H. A. Fields. 1996. 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. 50:5058.
40. Feinstone, S. M.,, A. Z. Kapikian,, and R. H. Purcell. 1973. Hepatitis A: detection by immune electron microscopy of a viruslike antigen associated with acute illness. Science 182:10261028.
41. Gane, E.,, R. Sallie,, M. Saleh,, B. Portmann,, and R. Williams. 1995. Clinical recurrence of hepatitis A following liver transplantation for acute liver failure. J. Med. Virol. 45:3539.
42. Gerolami, R.,, V. Moal,, and P. Colson. 2008. Chronic hepatitis E with cirrhosis in a kidney-transplant recipient. N. Engl. J. Med. 358:859860.
43. Ghabrah, T. M.,, S. Tsarev,, P. O. Yarbough,, S. U. Emerson,, G. T. Strickland,, and R. H. Purcell. 1998. Comparison of tests for antibody to hepatitis E virus. J. Med. Virol. 55:134137.
44. Graff, J.,, H. Nguyen,, C. Kasorndorkbua,, P. G. Halbur,, M. St,. Claire, R. H. Purcell, and S. U. Emerson. 2005. In vitro and in vivo mutational analysis of the 39-terminal regions of hepatitis E virus genomes and replicons. J. Virol. 79:10171026.
45. Graff, J.,, U. Torian,, H. Nguyen,, and S. U. Emerson. 2006. A bicistronic subgenomic mRNA encodes both the ORF2 and ORF3 proteins of hepatitis E virus. J. Virol. 80:59195926.
46. Guthmann, J. P.,, H. Klovstad,, D. Boccia,, N. Hamid,, L. Pinoges,, J. Y. Nizou,, M. Tatay,, F. Diaz,, A. Moren,, R. F. Grais,, I. Ciglenecki,, E. Nicand,, and P. J. Guerin. 2006. A large outbreak of hepatitis E among a displaced population in Darfur, Sudan, 2004: the role of water treatment methods. Clin. Infect. Dis. 42:16851691.
47. Haagsma, E. B.,, A. P. van den Berg,, R. J. Porte,, C. A. Benne,, H. Vennema,, J. H. Reimerink,, and M. P. Koopmans. 2008. Chronic hepatitis E virus infection in liver transplant recipients. Liver Transpl. 14:547553.
48. Hadler, S. C., 1991. Global impact of hepatitis A virus infection: changing patterns, p. 1420. In F. B. Hollinger,, S. M. Lemon,, and H. S. Margolis (ed.), Viral Hepatitis and Liver Disease. Williams & Wilkins, Baltimore, MD.
49. Halliday, M. L.,, L. Y. Kang,, T. K. Zhou,, M. D. Hu,, Q. C. Pan,, T. Y. Fu,, Y. S. Huang,, and S. L. Hu. 1991. An epidemic of hepatitis A attributable to the ingestion of raw clams in Shanghai, China. J. Infect. Dis. 164:852859.
50. Haqshenas, G.,, H. L. Shivaprasad,, P. R. Woolcock,, D. H. Read,, and X. J. Meng. 2001. 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. 82:24492462.
51. Hau, C. H.,, T. T. Hien,, N. T. Tien,, H. B. Khiem,, P. K. Sac,, V. T. Nhung,, R. P. Larasati,, K. Laras,, M. P. Putri,, R. Doss,, K. C. Hyams,, and A. L. Corwin. 1999. Prevalence of enteric hepatitis A and E viruses in the Mekong River delta region of Vietnam. Am. J. Trop. Med. Hyg. 60:277280.
52. He, J.,, A. W. Tam,, P. O. Yarbough,, G. R. Reyes,, and M. Carl. 1993. Expression and diagnostic utility of hepatitis E virus putative structural proteins expressed in insect cells. J. Clin. Microbiol. 31:21672173.
53. Hsieh, S. Y.,, X. J. Meng,, Y. H. Wu,, S. T. Liu,, A. W. Tam,, D. Y. Lin,, and Y. F. Liaw. 1999. Identity of a novel swine hepatitis E virus in Taiwan forming a monophyletic group with Taiwan isolates of human hepatitis E virus. J. Clin. Microbiol. 37:38283834.
54. Hsieh, S. Y.,, P. Y. Yang,, Y. P. Ho,, C. M. Chu,, and Y. F. Liaw. 1998. Identification of a novel strain of hepatitis E virus responsible for sporadic acute hepatitis in Taiwan. J. Med. Virol. 55:300304.
55. Hu, W. P.,, Y. Lu,, N. A. Precioso,, H. Y. Chen,, T. Howard,, D. Anderson,, and M. Guan. 2008. Double-antigen enzymelinked immunosorbent assay for detection of hepatitis E virus-specific antibodies in human or swine sera. Clin. Vaccine Immunol. 15:11511157.
56. Huang, F. F.,, Z. F. Sun,, S. U. Emerson,, R. H. Purcell,, H. L. Shivaprasad,, F. W. Pierson,, T. E. Toth,, and X. J. Meng. 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. 85:16091618.
57. Hutin, Y. J.,, V. Pool,, E. H. Cramer,, O. V. Nainan,, J. Weth,, I. T. Williams,, S. T. Goldstein,, K. F. Gensheimer,, B. P. Bell,, C. N. Shapiro,, M. J. Alter,, and H. S. Margolis for the National Hepatitis A Investigation Team. 1999. A multistate, foodborne outbreak of hepatitis A. N. Engl. J. Med. 340:595602.
58. Hyams, K. C.,, M. C. McCarthy,, M. Kaur,, M. A. Purdy,, D. W. Bradley,, M. M. Mansour,, S. Gray,, D. M. Watts,, and M. Carl. 1992. Acute sporadic hepatitis E in children living in Cairo, Egypt. J. Med. Virol. 37:274277.
59. Johnston, A.,, A. Macgregor,, S. Borovec,, M. Hattarki,, K. Stuckly,, D. Anderson,, N. H. Goss,, A. Oates,, and E. Uren. 2000. Inactivation and clearance of viruses during the manufacture of high purity factor IX. Biologicals 28:129136.
60. Kamar, N.,, J. Selves,, J. M. Mansuy,, L. Ouezzani,, J. M. Peron,, J. Guitard,, O. Cointault,, L. Esposito,, F. Abravanel,, M. Danjoux,, D. Durand,, J. P. Vinel,, J. Izopet,, and L. Rostaing. 2008. Hepatitis E virus and chronic hepatitis in organ-transplant recipients. N. Engl. J. Med. 358:811817.
61. Kar, P.,, S. Budhiraja,, A. Narang,, and A. Chakravarthy. 1997. Etiology of sporadic acute and fulminant non-A, non-B viral hepatitis in north India. Indian J. Gastroenterol. 16:4345.
62. Karetnyi, Y. V.,, M. J. Gilchrist,, and S. J. Naides. 1999. Hepatitis E virus infection prevalence among selected populations in Iowa. J. Clin. Virol. 14:5155.
63. Krawczynski, K. K.,, D. W. Bradley,, B. L. Murphy,, J. W. Ebert,, T. E. Anderson,, I. L. Doto,, A. Nowoslawski,, W. Duermeyer,, and J. E. Maynard. 1981. Pathogenetic aspects of hepatitis A virus infection in enterally inoculated marmosets. Am. J. Clin. Pathol. 76:698706.
64. Kwo, P. Y.,, G. G. Schlauder,, H. A. Carpenter,, P. J. Murphy,, J. E. Rosenblatt,, G. J. Dawson,, E. E. Mast,, K. Krawczynski,, and V. Balan. 1997. Acute hepatitis E by a new isolate acquired in the United States. Mayo Clin. Proc. 72:11331136.
65. Lemon, S. M. 1995. Hepatitis A virus and blood products: virus validation studies. Blood Coagul. Fibrinolysis 6(Suppl. 2):S20S22.
66. Lemon, S. M. 1994. The natural history of hepatitis A: the potential for transmission by transfusion of blood or blood products. Vox Sang. 4:1923.
67. Lemon, S. M.,, R. W. Jansen,, and J. E. Newbold. 1985. Infectious hepatitis A virus particles produced in cell culture consist of three distinct types with different buoyant densities in CsCl. J. Virol. 54:7885.
68. Li, F.,, J. Torresi,, S. A. Locarnini,, H. Zhuang,, W. Zhu,, X. Guo,, and D. A. Anderson. 1997. Amino-terminal epitopes are exposed when full-length open reading frame 2 of hepatitis E virus is expressed in Escherichia coli, but carboxy-terminal epitopes are masked. J. Med. Virol. 52:289300.
69. Li, F.,, H. Zhuang,, S. Kolivas,, S. Locarnini,, and D. Anderson. 1994. Persistent and transient antibody responses to hepatitis E virus detected by Western immunoblot using open reading frame 2 and 3 and glutathione S-transferase fusion proteins. J. Clin. Microbiol. 32:20602066.
70. Mast, E. E.,, M. J. Alter,, P. V. Holland,, and R. H. Purcell for the Hepatitis E Virus Antibody Serum Panel Evaluation Group. 1998. Evaluation of assays for antibody to hepatitis E virus by a serum panel. Hepatology 27:857861.
71. Matsubayashi, K.,, Y. Nagaoka,, H. Sakata,, S. Sato,, K. Fukai,, T. Kato,, K. Takahashi,, S. Mishiro,, M. Imai,, N. Takeda,, and H. Ikeda. 2004. Transfusion-transmitted hepatitis E caused by apparently indigenous hepatitis E virus strain in Hokkaido, Japan. Transfusion 44:934940.
72. McAtee, C. P.,, Y. Zhang,, P. O. Yarbough,, T. Bird,, and T. R. Fuerst. 1996. Purification of a soluble hepatitis E open reading frame 2-derived protein with unique antigenic properties. Protein Expr. Purif. 8:262270.
73. Meng, X.-J.,, R. H. Purcell,, P. G. Halbur,, J. R. Lehman,, D. M. Webb,, T. S. Tsareva,, J. S. Haynes,, B. J. Thacker,, and S. U. Emerson. 1997. A novel virus in swine is closely related to the human hepatitis E virus. Proc. Natl. Acad. Sci. USA 94:98609865.
74. Meng, X. J.,, P. G. Halbur,, J. S. Haynes,, T. S. Tsareva,, J. D. Bruna,, R. L. Royer,, R. H. Purcell,, and S. U. Emerson. 1998. Experimental infection of pigs with the newly identified swine hepatitis E virus (swine HEV), but not with human strains of HEV. Arch. Virol. 143:14051415.
75. Meng, X. J.,, P. G. Halbur,, M. S. Shapiro,, S. Govindarajan,, J. D. Bruna,, I. K. Mushahwar,, R. H. Purcell,, and S. U. Emerson. 1998. Genetic and experimental evidence for cross-species infection by swine hepatitis E virus. J. Virol. 72:97149721.
76. Mizuo, H.,, Y. Yazaki,, K. Sugawara,, F. Tsuda,, M. Takahashi,, T. Nishizawa,, and H. Okamoto. 2005. 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. 76:341349.
77. Mosley, J. W.,, M. J. Nowicki,, C. K. Kasper,, E. A. Operskalski,, E. Donegan,, L. M. Aledort,, M. W. Hilgartner, and The Transfusion Safety Study Group. 1994. Hepatitis A virus transmission by blood products in the United States. Vox Sang. 67(Suppl. 1):2428.
78. Myint, K. S.,, M. Guan,, H. Y. Chen,, Y. Lu,, D. Anderson,, T. Howard,, H. Noedl,, and M. P. Mammen, Jr. 2005. Evaluation of a new rapid immunochromatographic assay for serodiagnosis of acute hepatitis E infection. Am. J. Trop. Med. Hyg. 73:942946.
79. Nanda, S. K.,, I. H. Ansari,, S. K. Acharya,, S. Jameel,, and S. K. Panda. 1995. Protracted viremia during acute sporadic hepatitis E virus infection. Gastroenterology 108:225230.
80. Nanda, S. K.,, K. Yalcinkaya,, A. K. Panigrahi,, S. K. Acharya,, S. Jameel,, and S. K. Panda. 1994. Etiological role of hepatitis E virus in sporadic fulminant hepatitis. J. Med. Virol. 42:133137.
81. Payne, C. J.,, T. M. Ellis,, S. L. Plant,, A. R. Gregory,, and G. E. Wilcox. 1999. Sequence data suggests big liver and spleen disease virus (BLSV) is genetically related to hepatitis E virus. Vet. Microbiol. 68:119125.
82. Purcell, R. H.,, D. C. Wong,, and M. Shapiro. 2002. Relative infectivity of hepatitis A virus by the oral and intravenous routes in 2 species of nonhuman primates. J. Infect. Dis. 185:16681671.
83. Reid, T. M. S.,, and H. G. Robinson. 1987. Frozen raspberries and hepatitis A. Epidemiol. Infect. 98:109112.
84. Robertson, B. H.,, M. J. Alter,, B. P. Bell,, B. Evatt,, K. A. McCaustland,, C. N. Shapiro,, S. D. Sinha,, and J. M. Souci. 1998. Hepatitis A virus sequence detected in clotting factor concentrates associated with disease transmission. Biologicals 26:9599.
85. Rodriguez Lay, L. D. L. A.,, A. Quintana,, M. C. M. Villalba,, G. Lemos,, M. B. Corredor,, A. G. Moreno,, P. A. Prieto,, M. G. Guzman,, and D. Anderson. 2008. Dual infection with hepatitis A and E viruses in outbreaks and in sporadic clinical cases: Cuba 1998-2003. J. Med. Virol. 80:798802.
86. Rueckert, R. R., 1990. Picornaviridae and their replication, p. 507548. In B. N. Fields,, D. M. Knipe,, R. M. Chanock,, M. S. Hirsch,, J. L. Melnick,, T. P. Morath,, and B. Roizman (ed.), Virology, 2nd ed. Raven Press, New York, NY.
87. Schiodt, F. V.,, and W. M. Lee. 2003. Fulminant liver disease. Clin. Liver Dis. 7:331349, vi.
88. Schlauder, G. G.,, G. J. Dawson,, J. C. Erker,, P. Y. Kwo,, M. F. Knigge,, D. L. Smalley,, J. E. Rosenblatt,, S. M. Desai,, and I. K. Mushahwar. 1998. 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. 79:447456.
89. Schlauder, G. G.,, S. M. Desai,, A. R. Zanetti,, N. C. Tassopoulos,, and I. K. Mushahwar. 1999. Novel hepatitis E virus (HEV) isolates from Europe: evidence for additional genotypes of HEV. J. Med. Virol. 57:243251.
90. Schwartz, E.,, N. P. Jenks,, P. Van Damme,, and E. Galun. 1999. Hepatitis E virus infection in travelers. Clin. Infect. Dis. 29:13121314.
91. Seriwatana, J.,, M. P. Shrestha,, R. M. Scott,, S. A. Tsarev,, D. W. Vaughn,, K. S. Myint,, and B. L. Innis. 2002. Clinical and epidemiological relevance of quantitating hepatitis E virus-specific immunoglobulin M. Clin. Diagn. Lab. Immunol. 9:10721078.
92. Shaw, D. D.,, D. C. Whiteman,, A. D. Merritt,, D. M. El- Saadi,, R. J. Stafford,, K. Heel,, and G. A. Smith. 1999. Hepatitis A outbreaks among illicit drug users and their contacts in Queensland, 1997. Med. J. Aust. 170:584587.
93. Sheikh, A.,, M. Sugitani,, N. Kinukawa,, M. Moriyama,, Y. Arakawa,, K. Komiyama,, T. C. Li,, N. Takeda,, S. M. Ishaque,, M. Hasan,, and K. Suzuki. 2002. Hepatitis E virus infection in fulminant hepatitis patients and an apparently healthy population in Bangladesh. Am. J. Trop. Med. Hyg. 66:721724.
94. Shieh, Y.,, Y. Khudyakov,, G. Xia,, L. Ganova-Raeva,, F. Khambaty,, J. Woods,, M. Motes,, M. Glatzer,, S. Bialek,, and A. Fiore. 2007. Molecular confirmation of oysters as the vector for hepatitis A virus in a 2005 multistate outbreak. J. Food Prot. 70:145150.
95. Shrestha, M. P.,, R. M. Scott,, D. M. Joshi,, M. P. Mammen, Jr.,, G. B. Thapa,, N. Thapa,, K. S. Myint,, M. Fourneau,, R. A. Kuschner,, S. K. Shrestha,, M. P. David,, J. Seriwatana,, D. W. Vaughn,, A. Safary,, T. P. Endy,, and B. L. Innis. 2007. Safety and efficacy of a recombinant hepatitis E vaccine. N. Engl. J. Med. 356:895903.
96. Sjogren, M. H.,, H. Tanno,, O. Fay,, S. Sileoni,, B. D. Cohen,, D. S. Burke,, and R. J. Feighny. 1987. Hepatitis A virus in stool during clinical relapse. Ann. Intern. Med. 106:221226.
97. Snooks, M. J.,, P. Bhat,, J. Mackenzie,, N. A. Counihan,, N. Vaughan,, and D. A. Anderson. 2008. Vectorial entry and release of hepatitis A virus in polarized human hepatocytes. J. Virol. 82:87338742.
98. Sonoda, H.,, M. Abe,, T. Sugimoto,, Y. Sato,, M. Bando,, E. Fukui,, H. Mizuo,, M. Takahashi,, T. Nishizawa,, and H. Okamoto. 2004. Prevalence of hepatitis E virus (HEV) infection in wild boars and deer and genetic identification of a genotype 3 HEV from a boar in Japan. J. Clin. Microbiol. 42:53715374.
99. Staes, C. J.,, T. L. Schlenker,, I. Risk,, K. G. Cannon,, H. Harris,, A. T. Pavia,, C. N. Shapiro,, and B. P. Bell. 2000. Sources of infection among persons with acute hepatitis A and no identified risk factors during a sustained communitywide outbreak. Pediatrics 106:E54.
100. Stapleton, J. T.,, V. Raina,, P. L. Winokur,, K. Walters,, D. Klinzman,, E. Rosen,, and J. H. McLinden. 1993. Antigenic and immunogenic properties of recombinant hepatitis A virus 14S and 70S subviral particles. J. Virol. 67:10801085.
101. Takahashi, M.,, T. Nishizawa,, H. Miyajima,, Y. Gotanda,, T. Iita,, F. Tsuda,, and H. Okamoto. 2003. Swine hepatitis E virus strains in Japan form four phylogenetic clusters comparable with those of Japanese isolates of human hepatitis E virus. J. Gen. Virol. 84:851862.
102. Takahashi, M.,, K. Yamada,, Y. Hoshino,, H. Takahashi,, K. Ichiyama,, T. Tanaka,, and H. Okamoto. 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. 153:17031713.
103. Tanaka, T.,, M. Takahashi,, E. Kusano,, and H. Okamoto. 2007. Development and evaluation of an efficient cell-culture system for hepatitis E virus. J. Gen. Virol. 88:903911.
104. Tanaka, T.,, M. Takahashi,, H. Takahashi,, K. Ichiyama,, Y. Hoshino,, S. Nagashima,, H. Mizuo,, and H. Okamoto. 2009. Development and characterization of a genotype 4 hepatitis E virus cell culture system using a HE-JF5/15F strain recovered from a fulminant hepatitis patient. J. Clin. Microbiol. 47:19061910.
105. Thomas, D. L.,, P. O. Yarbough,, D. Vlahov,, S. A. Tsarev,, K. E. Nelson,, A. J. Saah,, and R. H. Purcell. 1997. Seroreactivity to hepatitis E virus in areas where the disease is not endemic. J. Clin. Microbiol. 35:12441247.
106. Tian, D. Y.,, Y. Chen,, and N. S. Xia. 2006. Significance of serum IgA in patients with acute hepatitis E virus infection. World J. Gastroenterol. 12:39193923.
107. Tilzey, A. J.,, S. J. Palmer,, S. Barrow,, K. R. Perry,, H. Tyrell,, A. Safary,, and J. E. Banatvala. 1992. Effect of hepatitis A vaccination schedules on immune response. Vaccine 10(Suppl. 1):S121S123.
108. Tsarev, S. A.,, T. S. Tsareva,, S. U. Emerson,, S. Govindarajan,, M. Shapiro,, J. L. Gerin,, and R. H. Purcell. 1997. Recombinant vaccine against hepatitis E: dose response and protection against heterologous challenge. Vaccine 15:18341838.
109. Tsarev, S. A.,, T. S. Tsareva,, S. U. Emerson,, S. Govindarajan,, M. Shapiro,, J. L. Gerin,, and R. H. Purcell. 1994. Successful passive and active immunization of cynomolgus monkeys against hepatitis E. Proc. Natl. Acad. Sci. USA 91:1019810202.
110. Tsarev, S. A.,, T. S. Tsareva,, S. U. Emerson,, P. O. Yarbough,, L. J. Legters,, T. Moskal,, and R. H. Purcell. 1994. Infectivity titration of a prototype strain of hepatitis E virus in cynomolgus monkeys. J. Med. Virol. 43:135142.
111. van Cuyck, H.,, F. Juge,, and P. Roques. 2003. Phylogenetic analysis of the first complete hepatitis E virus (HEV) genome from Africa. FEMS Immunol. Med. Microbiol. 39:133139.
112. Van Doorslaer, E.,, G. Tormans,, and P. Van Damme. 1994. Cost-effectiveness analysis of vaccination against hepatitis A in travellers. J. Med. Virol. 44:463469.
113. Vento, S.,, T. Garofano,, C. Renzini,, F. Cainelli,, F. Casali,, G. Ghironzi,, T. Ferraro,, and E. Concia. 1998. Fulminant hepatitis associated with hepatitis A virus superinfection in patients with chronic hepatitis C. N. Engl. J. Med. 338:286290.
114. Wang, Y. 1992. Study on diagnosis of hepatitis A by testing salivary IgM anti-HAV. Zhonghua Liu Xing Bing Xue Za Zhi 13:911.
115. Wang, Y.,, R. Ling,, J. C. Erker,, H. Zhang,, H. Li,, S. Desai,, I. K. Mushahwar,, and T. J. Harrison. 1999. A divergent genotype of hepatitis E virus in Chinese patients with acute hepatitis. J. Gen. Virol. 80:169177.
116. Wheeler, C.,, T. M. Vogt,, G. L. Armstrong,, G. Vaughan,, A. Weltman,, O. V. Nainan,, V. Dato,, G. Xia,, K. Waller,, J. Amon,, T. M. Lee,, A. Highbaugh-Battle,, C. Hembree,, S. Evenson,, M. A. Ruta,, I. T. Williams,, A. E. Fiore,, and B. P. Bell. 2005. An outbreak of hepatitis A associated with green onions. N. Engl. J. Med. 353:890897.
117. Yamada, K.,, M. Takahashi,, Y. Hoshino,, H. Takahashi,, K. Ichiyama,, T. Tanaka,, and H. Okamoto. 2009. Construction of an infectious cDNA clone of hepatitis E virus strain JE03-1760F that can propagate efficiently in cultured cells. J. Gen. Virol. 90:457462.
118. Yarbough, P. O.,, E. Garza,, A. W. Tam,, Y. Zhang,, P. McAtee,, and T. R. Fuerst,. 1996. Assay development of diagnostic tests for IgM and IgG antibody to hepatitis E virus, p. 294296. In Y. Buisson,, P. Coursaget,, and M. Kane (ed.), Enterically-Transmitted Hepatitis Viruses. La Simarre, Joueles-Tours, France.
119. Yarbough, P. O.,, A. W. Tam,, K. Gabor,, E. Garza,, R. A. Moeckli,, I. Palings,, C. Simonsen,, and G. R. Reyes,. 1994. Assay development of diagnostic tests for hepatitis E, p. 367370. In K. Nishioka,, H. Suzuki,, S. Mishiro,, and T. Oda (ed.), Viral Hepatitis and Liver Disease. Springer-Verlag, Tokyo, Japan.
120. Yazaki, Y.,, H. Mizuo,, M. Takahashi,, T. Nishizawa,, N. Sasaki,, Y. Gotanda,, and H. Okamoto. 2003. Sporadic acute or fulminant hepatitis E in Hokkaido, Japan, may be foodborne, as suggested by the presence of hepatitis E virus in pig liver as food. J. Gen. Virol. 84:23512357.
121. Yu, C.,, R. E. Engle,, J. P. Bryan,, S. U. Emerson,, and R. H. Purcell. 2003. Detection of immunoglobulin M antibodies to hepatitis E virus by class capture enzyme immunoassay. Clin. Diagn. Lab. Immunol. 10:579586.
122. Zanetti, A. R.,, G. G. Schlauder,, L. Romano,, E. Tanzi,, P. Fabris,, G. J. Dawson,, and I. K. Mushahwar. 1999. Identification of a novel variant of hepatitis E virus in Italy. J. Med. Virol. 57:356360.
123. Zhang, M.,, S. U. Emerson,, H. Nguyen,, R. E. Engle,, S. Govindarajan,, J. L. Gerin,, and R. H. Purcell. 2001. Immunogenicity and protective efficacy of a vaccine prepared from 53 kDa truncated hepatitis E virus capsid protein expressed in insect cells. Vaccine 20:853857.
124. Zhang, S.,, D. Tian,, Z. Zhang,, J. Xiong,, Q. Yuan,, S. Ge,, J. Zhang,, and N. Xia. 2009. Clinical significance of anti-HEV IgA in diagnosis of acute genotype 4 hepatitis E virus infection negative for anti-HEV IgM. Dig. Dis. Sci. 54:25122518.
125. Zhou, Y. H.,, R. H. Purcell,, and S. U. Emerson. 2005. A truncated ORF2 protein contains the most immunogenic site on ORF2: antibody responses to non-vaccine sequences following challenge of vaccinated and non-vaccinated macaques with hepatitis E virus. Vaccine 23:31573165.
126. Zhou, Y. H.,, R. H. Purcell,, and S. U. Emerson. 2004. An ELISA for putative neutralizing antibodies to hepatitis E virus detects antibodies to genotypes 1, 2, 3, and 4. Vaccine 22:25782585.

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error