Molecular characterization of hepatitis C and E viruses

  • D. W. Bradley
  • M. J. Beach
  • M. A. Purdy
Part of the Archives of Virology book series (ARCHIVES SUPPL, volume 7)


The molecular features of each of the major viruses of non-A, non-B hepatitis, namely hepatitis C virus (HCV) and hepatitis E virus (HEV) are briefly described. The organization of the genome of each of these viruses is discussed and compared to those of other related or distantly related viruses that contain single-stranded, positive-sense RNA genomes. HCV has been tentatively classified as a separate genus within the Flaviviridae, whereas HEV has been loosely associated with caliciviruses and subsequently assigned to the Caliciviridae, although it does possess unique genetic features not found in other caliciviruses.


Unique Genetic Feature Extreme Carboxy Terminus 
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  1. 1.
    Alter MJ, Hadler SC, Judson FN, Mares A, Alexander WJ, Hu PY, Miller JK, Moyer LA, Fields HA, Bradley DW, Margolis HS (1990) Risk factors for acute non-A, non-B hepatitis in the United States and association with hepatitis C virus infection. JAMA 264: 2231–2235PubMedCrossRefGoogle Scholar
  2. 2.
    Argos P (1988) A sequence motif in many polymerases. Nucleic Acids Res 16: 9909–9916PubMedCrossRefGoogle Scholar
  3. 3.
    Beach M, Bradley D (1991) Analysis of the putative nonstructural gene region of hepatitis C virus. In: Hollinger FB, Lemon S, Margolis H (eds) Viral hepatitis and liver disease. Williams and Wilkins, Baltimore, pp 376–381Google Scholar
  4. 4.
    Beach MJ, Meeks EL, Mimms LT, Vallari D, DuCharme L, Spelbring J, Taskar S, Schleicher JB, Krawczynski K, Bradley DW (1992) Temporal relationships of hepatitis C virus RNA and antibody responses following experimental infection of chimpanzees. J Med Virol 36: 226–237PubMedCrossRefGoogle Scholar
  5. 5.
    Bradley DW (1990) Hepatitis non-A, non-B viruses become identified as hepatitis C and E viruses. In: Melnick JL (ed) Progress in medical virology, vol 37. S. Karger AG, Basel, pp 101–135Google Scholar
  6. 6.
    Bradley DW (1990) Enterically-transmitted non-A, non-B hepatitis. Br Med Bull 46: 442–461PubMedGoogle Scholar
  7. 7.
    Bradley DW, Krawcsynski K, Beach MJ, Purdy MA (1991) Non-A, non-B hepatitis: Toward the discovery of hepatitis C and E viruses. Semin Liver Dis 11: 128–146Google Scholar
  8. 8.
    Bradley DW, Andjaparidze A, Cook EH, McCaustland K, Balayan M, Stetler H, Velazquez O, Robertson B, Humphrey C, Kane M, Weisfuse I (1988) Aetiological agent of enterically-transmitted non-A, non-B hepatitis. J Gen Virol 69: 731–738PubMedCrossRefGoogle Scholar
  9. 9.
    Chambers TJ, McCourt DW, Rice CM (1989) Yellow fever virus proteins NS2A, NS2B, and NS4B: identification and partial N-terminal amino acid sequence analysis. Virology 169: 100–109PubMedCrossRefGoogle Scholar
  10. 10.
    Choo Q-L, Kuo G, Weiner AJ, Overby LR, Bradley DW, Houghton M (1989) Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science 244: 359–362PubMedCrossRefGoogle Scholar
  11. 11.
    Choo Q-L, Richman KH, Han JH, Berger K, Lee C, Dong D, Gallegos C, Coit D, Medina-Selby A, Bar PJ, Weiner AJ, Bradley DW (1991) Genetic organization and diversity of the hepatitis C virus. Proc Natl Acad Sci USA 88: 2451–2455PubMedCrossRefGoogle Scholar
  12. 12.
    Farci P, Alter HJ, Wong D, Miller RH, Shih JW, Jett B, Purcell RH (1991) A long-term study of hepatitis C virus replication in non-A, non-B hepatitis. N Engl J Med 325: 98–104PubMedCrossRefGoogle Scholar
  13. 13.
    Fong T-L, Shindo M, Feinstone SM, Hoofnagle JH, DiBiscegli AM (1991) Detection of replicative intermediates of hepatitis C viral RNA in liver and serum of patients with chronic hepatitis C. J Clin Invest 88: 1058–1060PubMedCrossRefGoogle Scholar
  14. 14.
    Fry KE, Tam AW, Smith MM, Kim JP, Luk K-C, Young LM, Paatak M, Feldman RA, Yun KY, Purdy MA, McCaustland KA, Bradley DW, Reyes GR (1991) Hepatitis E virus (HEV): Strain variation in the nonstructural gene region encoding motifs for an RNA-dependent RNA polymerase and an ATP/GTP binding site. Virus Genes 6: 173–185Google Scholar
  15. 15.
    Gorbalenya AE, Donchenko AP, Koonin EV, Blinov VM (1989) N-terminal domains of putative helicases of flavi-and pestiviruses may be serine proteases. Nucleic Acids Res 17: 3889–3897PubMedCrossRefGoogle Scholar
  16. 16.
    Gorbalenya AE, Koonin EV, Donchenko AP, Blinov VM (1989) Two related superfamilies of putative helicases involved in replication, recombination, repair and expression of DNA and RNA genomes. Nucleic Acids Res 17: 4713–4730PubMedCrossRefGoogle Scholar
  17. 17.
    Han JH, Shyamala V, Richman KH, Brauer MJ, Irvine B, Urdea MS, TekampOlson P, Kuo G, Choo Q-L, Houghton M (1991) Characterization of the terminal regions of hepatitis C viral RNA: Identification of conserved sequences in the 5’ untranslated region and poly(A) tails at the 3’ end. Proc Natl Acad Sci USA 88: 1711–1715PubMedCrossRefGoogle Scholar
  18. 18.
    Hijikata M, Kato N, Ootsuyama Y, Nakagawa M, Shimotohno K (1991) Gene mapping of the putative structural region of the hepatitis C virus genome by in vitro processing analysis. Proc Natl Acad Sci USA 88: 5547–5551PubMedCrossRefGoogle Scholar
  19. 19.
    Holland JJ (1991) Defective viral genomes. In: Fields BN, Knipe DN (eds) Fundamental virology. Raven Press, New York, pp 151–165Google Scholar
  20. 20.
    Houghton M, Weiner A, Han J, Kuo G, Choo Q-L (1991) Molecular biology of the hepatitis C viruses: Implications for diagnosis, development, and control of viral disease. Hepatology 14: 381–388Google Scholar
  21. 21.
    Jiang X, Graham DY, Wang K, Estes, MK (1990) Norwalk virus genome cloning and characterization. Science 250: 1580–1583CrossRefGoogle Scholar
  22. 22.
    Kato N, Hijikata M, Ootsuyama Y, Nakagawa M, Ohkoshi S, Sugiyama T, Shimotohno K (1990) Molecular cloning of the human hepatitis C virus genome from Japanese patients with non-A, non-B hepatitis. Proc Natl Acad Sci USA 87: 9524–9528PubMedCrossRefGoogle Scholar
  23. 23.
    Kaur M, Hyams KC, Purdy MA, Krawczynski K, Ching WM, Fry KE, Reyes GR, Bradley DW, Carl M (1992) Human linear B-cell epitopes encoded by the hepatitis E virus include determinants in the RNA-dependent RNA polymerase. Proc Natl Acad Sci USA 89: 3855–3858Google Scholar
  24. 24.
    Koonin EV, Gorbalenya AE, Purdy MA, Rozanov MN, Reyes GR, Bradley DW (1992) Computer-assisted assignment of functional domains in the nonstructural polyprotein of hepatitis E virus: Delineation of an additional group of positive-strand RNA plant and animal viruses. Proc Natl Acad Sci USA 89: 8259–8263Google Scholar
  25. 25.
    Krawczynski K, Beach MJ, Bradley DW, Kuo G, DiBiscegli AM, Houghton M, Reyes GR, Kim JP, Choo Q-L, Alter MJ (1992) Hepatitis C virus antigen in hepatocytes: Immunomorphologic detection and identification. Gastroenterology 103: 622–629Google Scholar
  26. 26.
    Krawczynski K, Bradley D, Ajdukiewicz A, Alter MV, Caredda F, Dilawari J, Hlady G, Innis B, Kane M, Nasidi A, Redeker A, Stetler H, Toukan A, Yoffee B (1991) Virus-associated antigen and antibody of epidemic non-A, non-B hepatitis: Serology of outbreaks and sporadic cases. In: Shikata T, Purcell RH, Uchida T (eds) Viral hepatitis C, D, and E. Elsevier Science, Amsterdam, pp 229–236Google Scholar
  27. 27.
    Lain S, Riechmann JL, Garcia JA (1990) RNA helicase: a novel activity associated with a protein encoded by a positive strand RNA virus. Nucleic Acids Res 18: 7003–7006PubMedCrossRefGoogle Scholar
  28. 28.
    Martell M, Esteban JI, Quer J, Genesca J, Weiner A, Esteban R, Guardia J, Gomez J (1992) Hepatitis C virus (HCV) circulates as a population of different but closely related genomes: Quasispecies nature of HCV genome distribution. J Virol 66: 3225–3229Google Scholar
  29. 29.
    Miller RH, Purcell RH (1990) Hepatitis C virus shares amino acid sequence similarity with pestiviruses and flaviviruses as well as members of two plant virus supergroups. Proc Natl Acad Sci USA 87: 2057–2061PubMedCrossRefGoogle Scholar
  30. 30.
    Preugschat F, Yao C-W, Strauss JH (1990) In vitro processing of dengue virus type 2 nonstructural proteins NS2A, NS2B, and NS3. J Virol 64: 4364–4374Google Scholar
  31. 31.
    Prince AM, Brotman B, Huima T, Pascual D, Jaffery M, Inchauspe G (1992) Immunity in hepatitis C infection. J Infect Dis 165: 438–443PubMedCrossRefGoogle Scholar
  32. 32.
    Purdy MA, McCaustland KA, Krawczynski K, Tam A, Beach MJ, Tassopoulos NC, Reyes GR, Bradley DW (1992) Expression of a hepatitis E virus (HEV)-trpE fusion protein containing epitopes recognized by antibodies in sera from human cases and experimentally infected primates. Arch Virol 123: 335–349PubMedCrossRefGoogle Scholar
  33. 33.
    Reyes GR, Purdy MA, Kim JP, Luk K-C, Young LM, Frey KE, Bradley DW (1990) Isolation of a cDNA from the virus responsible for enterically transmitted non-A, non-B hepatitis. Science 247: 1335–1339PubMedCrossRefGoogle Scholar
  34. 34.
    Reyes GR, Kim JP (1991) Sequence-independent, single-primer amplification ( SISPA) of complex DNA populations. Mol Cell Probes 5: 473–481Google Scholar
  35. 35.
    Reyes GR, Huang C-C, Yarbough PO, Young LM, Tam AW, Moeckli RA, Yun KY, Nguyen D, Smith MM, Fernandez J, Guerra ME, Kim JP, Luk K-C, Drawczynski K, Purdy MA, Fry KE, Bradley DW (1991) Hepatitis E virus (HEV): Epitope mapping and detection of strain variation. In: Shikata T, Purcell RH, Uchida T (eds) Viral hepatitis C, D, and E. Elsevier Science, Amsterdam, pp 237–245Google Scholar
  36. 36.
    Shimizu YK, Weiner AJ, Rosenblatt J, Wong DC, Sapiro M, Popkin T, Houghton M, Alter HJ, Purcell RH (1990) Early events in hepatitis C virus infection of chimpanzees. Proc Natl Acad Sci USA 87: 6441–6444PubMedCrossRefGoogle Scholar
  37. 37.
    Tam AW, Smith MM, Guerra ME, Huang CC, Bradley DW, Fry KE, Reyes GR (1991) Hepatitis E virus (HEV): Molecular cloning and sequencing of the full-length viral genome. Virology 185: 120–131Google Scholar
  38. 38.
    Tohya Y, Taniguchi Y, Utagawa E, Takeda N, Miyamura K, Yamazaki S, Mikami T (1991) Sequence analysis of the 3’ end of feline calicivirus genome. Virology 183: 810–814PubMedCrossRefGoogle Scholar
  39. 39.
    Tsukiyama-Kohara K, Iizuka N, Kohara M, Nomoto A (1992) Internal ribosome entry site within hepatitis C virus RNA. J Virol 66: 1476–1483PubMedGoogle Scholar
  40. 40.
    Weiner AJ, Kuo G, Bradley DW, Bonino F, Saracco G, Lee C, Rosenblatt J, Choo Q-L, Houghton M (1990) Detection of hepatitis C viral sequences in non-A, non-B hepatitis. Lancet 335: 1–3PubMedCrossRefGoogle Scholar
  41. 41.
    Weiner AJ, Brauer MJ, Rosenblatt J, Richman KH, Tung J, Crawford F, Bonino F, Saracco G, Choo Q-L, Houghton M, Han JH (1991) Variable and hypervariable domains are found in the regions of HCV corresponding to the flavivirus envelope and NS1 proteins and the pestivirus envelope glycoproteins. Virology 180: 842–848PubMedCrossRefGoogle Scholar
  42. 42.
    Wengler G, Wengler G (1991) The carboxy-terminal part of the NS3 protein of the west nile flavivirus can be isolated as a soluble protein after proteolytic cleavage and represents an RNA-stimulated NTPase. Virology 184: 707–715PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 1993

Authors and Affiliations

  • D. W. Bradley
    • 1
    • 2
  • M. J. Beach
    • 1
  • M. A. Purdy
    • 1
  1. 1.Hepatitis Branch, Mailstop A33, DVRDNCID, Centers for Disease ControlAtlantaUSA
  2. 2.Hepatitis Branch, Division of Viral and Rickettsial DiseasesNational Center for Infectious Diseases, Centers for Disease ControlAtlantaUSA

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