Isolates of hepatitis E virus (HEV) have recently been described from China that are distinct from Burmese, Mexican and US viruses and constitute a novel genotype (genotype 4). Here, the complete genomic sequence of a representative isolate of genotype 4 HEV, amplified directly from the stool of an acutely infected patient, is presented. Analysis of the entire sequence confirms our previous conclusion, based upon partial sequence data, that these Chinese isolates belong to a novel genotype. Typical of genetic variation in HEV, most nucleotide substitutions occur in the third base of the codon and do not affect the amino acid sequence. The genotype 4 virus is unusual in that a single nucleotide insertion in the ORF 3 region changes the initiation of ORF 3, and perhaps also ORF 2. The consequences of these changes are discussed.


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  1. Aye, T. T., Uchida, T., Ma, X., Iida, F., Shikata, T., Ichikawa, M., Rikihisa, T. & Win, K. M. (1993). Sequence and gene structure of the hepatitis E virus isolated from Myanmar. Virus Genes 7, 95-110.[CrossRef] [Google Scholar]
  2. Bi, S. L., Purdy, M. A., McCaustland, K. A., Margolis, H. S. & Bradley, D. W. (1993). The sequence of hepatitis E virus isolated directly from a single source during an outbreak in China. Virus Research 28, 233-247.[CrossRef] [Google Scholar]
  3. Bradley, D. W. (1992). Hepatitis E: epidemiology, aetiology and molecular biology. Reviews in Medical Virology 2, 19-28.[CrossRef] [Google Scholar]
  4. Buisson, Y., Grandadam, M., Nicand, E., Cheval, P., van Cuyck-Gandre, H., Innis, B., Rehel, P., Coursaget, P., Teyssou, R. & Tsarev, S. (2000). Identification of a novel hepatitis E virus in Nigeria. Journal of General Virology 81, 903-909. [Google Scholar]
  5. Chatterjee, R., Tsarev, S., Pillot, J., Coursaget, P., Emerson, S. U. & Purcell, R. H. (1997). African strains of hepatitis E virus that are distinct from Asian strains. Journal of Medical Virology 53, 139-144.[CrossRef] [Google Scholar]
  6. Clayson, E. T., Innis, B. L., Myint, K. S., Narupiti, S., Vaughn, D. W., Giri, S., Ranabhat, P. & Shrestha, M. P. (1995). Detection of hepatitis E virus infections among domestic swine in the Kathmandu Valley of Nepal. American Journal of Tropical Medicine and Hygiene 53, 228-232. [Google Scholar]
  7. Dawson, G. J., Chau, K. H., Cabal, C. M., Yarbough, P. O., Reyes, G. R. & Mushahwar, I. K. (1992). Solid-phase enzyme-linked immunosorbent assay for hepatitis E virus IgG and IgM antibodies utilizing recombinant antigens and synthetic peptides. Journal of Virological Methods 38, 175-186.[CrossRef] [Google Scholar]
  8. Donati, M. C., Fagan, E. A. & Harrison, T. J. (1997). Sequence analysis of full length HEV clones derived directly from human liver in fulminant hepatitis E. In Viral Hepatitis and Liver Disease, pp. 313-316. Edited by M. Rizzetto, R. H. Purcell, J. L. Gerin & G. Verme. Torino: Edizioni Minerva Medica.
  9. Felsenstein, J. (1993). PHYLIP inference package version 3.5c. Department of Genetics, University of Washington, Seattle, WA, USA.
  10. Harrison, T. J. (1999). Hepatitis E virus – an update. Liver 19, 171-176. [Google Scholar]
  11. Hsieh, S. Y., Yang, P. Y., Ho, Y. P., Chu, C. M. & Liaw, Y. F. (1998). Identification of a novel strain of hepatitis E virus responsible for sporadic acute hepatitis in Taiwan. Journal of Medical Virology 55, 300-304.[CrossRef] [Google Scholar]
  12. Huang, C. C., Nguyen, D., Fernandez, J., Yun, K. Y., Fry, K. E., Bradley, D. W., Tam, A. W. & Reyes, G. R. (1992). Molecular cloning and sequencing of the Mexico isolate of hepatitis E virus (HEV). Virology 191, 550-558.[CrossRef] [Google Scholar]
  13. Huang, R. T., Nakazono, N., Ishii, K., Kawamata, O., Kawaguchi, R. & Tsukada, Y. (1995). II. Existing variations on the gene structure of hepatitis E virus strains from some regions of China.Journal of Medical Virology 47, 303-308.[CrossRef] [Google Scholar]
  14. Kaur, M., Hyams, K. C., Purdy, M. A., Krawczynski, K., Ching, W. M., Fry, K. E., Reyes, G. R., Bradley, D. W. & Carl, M. (1992). Human linear B-cell epitopes encoded by the hepatitis E virus include determinants in the RNA-dependent RNA polymerase. Proceedings of the National Academy of Sciences, USA 89, 3855-3858.[CrossRef] [Google Scholar]
  15. Khudyakov, Y. E., Favorov, M. O., Jue, D. L., Hine, T. K. & Fields, H. A. (1994a). Immunodominant antigenic regions in a structural protein of the hepatitis E virus. Virology 198, 390-393.[CrossRef] [Google Scholar]
  16. Khudyakov, Y. E., Favorov, M. O., Khudyakova, N. S., Cong, M. E., Holloway, B. P., Padhye, N., Lambert, S. B., Jue, D. L. & Fields, H. A. (1994b). Artificial mosaic protein containing antigenic epitopes of hepatitis E virus. Journal of Virology 68, 7067-7074. [Google Scholar]
  17. Koonin, E. V., Gorbalenya, A. E., Purdy, M. A., Rozanov, M. N., Reyes, G. R. & Bradley, D. W. (1992). Computer-assisted assignment of functional domains in the nonstructural polyprotein of hepatitis-e virus – delineation of an additional group of positive-strand RNA plant and animal viruses. Proceedings of the National Academy of Sciences, USA 89, 8259-8263.[CrossRef] [Google Scholar]
  18. Kwo, P. Y., Schlauder, G. G., Carpenter, H. A., Murphy, P. J., Rosenblatt, J. E., Dawson, G. J., Mast, E. E., Krawczynski, K. & Balan, V. (1997). Acute hepatitis E by a new isolate acquired in the United States. Mayo Clinic Proceedings 72, 1133-1136.[CrossRef] [Google Scholar]
  19. Li, K., Zhuang, H. & Zhu, W. (2000). Partial nucleotide sequencing of hepatitis E viruses isolated from 14 cities of China: identification of 2 major variants of hepatitis E virus. Journal of Medical Virology (in press).
  20. Mast, E. E., Alter, M. J. & Holland, P. V. (1998). Evaluation of assays for antibody to hepatitis E virus by a serum panel. Hepatology 27, 856-861. [Google Scholar]
  21. Meng, X. J., Purcell, R. H., Halbur, P. G., Lehman, J. R., Webb, D. M., Tsareva, T. S., Haynes, J. S., Thacker, B. J. & Emerson, S. U. (1997). A novel virus in swine is closely related to the human hepatitis E virus. Proceedings of the National Academy of Sciences, USA 94, 9860-9865.[CrossRef] [Google Scholar]
  22. Meng, X. J., Halbur, P. G., Shapiro, M. S., Govindarajan, S., Bruna, J. D., Mushahwar, I. K., Purcell, R. H. & Emerson, S. U. (1998). Genetic and experimental evidence for cross-species infection by swine hepatitis E virus. Journal of Virology 72, 9714-9721. [Google Scholar]
  23. Nielsen, H., Engelbrecht, J., von Heijne, G. & Brunak, S. (1996). Defining a similarity threshold for a functional protein sequence pattern: the signal peptide cleavage site. Proteins 24, 165-177.[CrossRef] [Google Scholar]
  24. Panda, S. K., Nanda, S. K., Zafrullah, M., Ansari, I. U. H., Ozdener, M. H. & Jameel, S. (1995). 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. Journal of Clinical Microbiology 33, 2653-2659. [Google Scholar]
  25. Reyes, G. R., Purdy, M. A., Kim, J. P., Luk, K. C., Young, L. M., Fry, K. E. & Bradley, D. W. (1990). Isolation of a cDNA from the virus responsible for enterically transmitted non-A, non-B hepatitis. Science 247, 1335-1339.[CrossRef] [Google Scholar]
  26. Schlauder, G. G., Dawson, G. J., Erker, J. C., Kwo, P. Y., Knigge, M. F., Smalley, D. L., Rosenblatt, J. E., Desai, S. M. & Mushahwar, I. K. (1998). The sequence and phylogenetic analysis of a novel hepatitis E virus isolated from a patient with acute hepatitis reported in the United States. Journal of General Virology 79, 447-456. [Google Scholar]
  27. Schlauder, G. G., Desai, S. M., Zanetti, A. R., Tassopoulos, N. C. & Mushahwar, I. K. (1999). Novel hepatitis E virus (HEV) isolates from Europe: evidence for additional genotypes of HEV. Journal of Medical Virology 57, 243-251.[CrossRef] [Google Scholar]
  28. Tam, A. W., Smith, M. M., Guerra, M. E., Huang, C. C., Bradley, D. W., Fry, K. E. & Reyes, G. R. (1991). Hepatitis E virus (HEV): molecular cloning and sequencing of the full-length viral genome. Virology 185, 120-131.[CrossRef] [Google Scholar]
  29. Torresi, J., Li, F., Locarnini, S. A. & Anderson, D. A. (1999). Only the non-glycosylated fraction of hepatitis E virus capsid (open reading frame 2) protein is stable in mammalian cells. Journal of General Virology 80, 1185-1188. [Google Scholar]
  30. Tsarev, S. A., Emerson, S. U., Reyes, G. R., Tsareva, T. S., Legters, L. J., Malik, I. A. & Purcell, R. H. (1992). Characterization of a prototype strain of hepatitis E virus. Proceedings of the National Academy of Sciences, USA 89, 559-563.[CrossRef] [Google Scholar]
  31. Wang, Y. C., Ling, R., Erker, J. C., Zhang, H. Y., Li, H. M., Desai, S., Mushahwar, I. K. & Harrison, T. J. (1999). A divergent genotype of hepatitis E virus in Chinese patients with acute hepatitis. Journal of General Virology 80, 169-177. [Google Scholar]
  32. Wu, J. C., Sheen, I. J., Chiang, T. Y., Sheng, W. Y., Wang, Y. J., Chan, C. Y. & Lee, S. D. (1998). The impact of travelling to endemic areas on the spread of hepatitis E virus infection: epidemiological and molecular analyses. Hepatology 27, 1415-1420.[CrossRef] [Google Scholar]
  33. Yang, J., Zhang, H., Wang, Y., Mao, Q. & Li, H. (2000). Partial sequence comparison of three sporadic hepatitis E variants. Chinese Journal of Virology (in press).
  34. Yarbough, P. O., Tam, A. W., Fry, K. E., Krawczynski, K., McCaustland, K. A., Bradley, D. W. & Reyes, G. R. (1991). Hepatitis E virus: identification of type-common epitopes. Journal of Virology 65, 5790-5797. [Google Scholar]
  35. Yin, S. R., Purcell, R. H. & Emerson, S. U. (1994). A new Chinese isolate of hepatitis E virus: comparison with strains recovered from different geographical regions. Virus Genes 9, 23-32.[CrossRef] [Google Scholar]

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