Skip to main content
NCBI home page
Journal of Virology logoLink to Journal of Virology
. 1991 Mar;65(3):1105–1113. doi: 10.1128/jvi.65.3.1105-1113.1991

Structure and organization of the hepatitis C virus genome isolated from human carriers.

A Takamizawa 1, C Mori 1, I Fuke 1, S Manabe 1, S Murakami 1, J Fujita 1, E Onishi 1, T Andoh 1, I Yoshida 1, H Okayama 1
PMCID: PMC239876  PMID: 1847440

Abstract

Hepatitis C virus (HCV) is a major causative agent of posttransfusion non-A, non-B hepatitis, which often develops into malignant chronic diseases, including liver cirrhosis and hepatocellular carcinoma. We have cloned from human carriers overlapping cDNAs (9,416 bp) covering the entire coding region of the HCV genome. The latter encodes a 3,010-amino-acid polyprotein. In addition, there are 332 and 54 bases of 5' and 3' noncoding sequences, respectively. Our HCV strain has a 77% nucleic acid identity to the HCV strain cloned by workers at Chiron Corporation. The hydrophobicity profile of the putative polyprotein is similar to those of flaviviruses, but it has limited amino acid homology to polyproteins of flaviviruses and other viruses, indicating that HCV is at most distantly related to flaviviruses.

Full text

PDF
1105

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Benton W. D., Davis R. W. Screening lambdagt recombinant clones by hybridization to single plaques in situ. Science. 1977 Apr 8;196(4286):180–182. doi: 10.1126/science.322279. [DOI] [PubMed] [Google Scholar]
  2. Bradley D. W., Maynard J. E., Popper H., Cook E. H., Ebert J. W., McCaustland K. A., Schable C. A., Fields H. A. Posttransfusion non-A, non-B hepatitis: physicochemical properties of two distinct agents. J Infect Dis. 1983 Aug;148(2):254–265. doi: 10.1093/infdis/148.2.254. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bradley D. W., McCaustland K. A., Cook E. H., Schable C. A., Ebert J. W., Maynard J. E. Posttransfusion non-A, non-B hepatitis in chimpanzees. Physicochemical evidence that the tubule-forming agent is a small, enveloped virus. Gastroenterology. 1985 Mar;88(3):773–779. [PubMed] [Google Scholar]
  4. Castle E., Leidner U., Nowak T., Wengler G., Wengler G. Primary structure of the West Nile flavivirus genome region coding for all nonstructural proteins. Virology. 1986 Feb;149(1):10–26. doi: 10.1016/0042-6822(86)90082-6. [DOI] [PubMed] [Google Scholar]
  5. Choo Q. L., Kuo G., Weiner A. J., Overby L. R., Bradley D. W., Houghton M. Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science. 1989 Apr 21;244(4902):359–362. doi: 10.1126/science.2523562. [DOI] [PubMed] [Google Scholar]
  6. Colett M. S., Larson R., Gold C., Strick D., Anderson D. K., Purchio A. F. Molecular cloning and nucleotide sequence of the pestivirus bovine viral diarrhea virus. Virology. 1988 Jul;165(1):191–199. doi: 10.1016/0042-6822(88)90672-1. [DOI] [PubMed] [Google Scholar]
  7. Domier L. L., Franklin K. M., Shahabuddin M., Hellmann G. M., Overmeyer J. H., Hiremath S. T., Siaw M. F., Lomonossoff G. P., Shaw J. G., Rhoads R. E. The nucleotide sequence of tobacco vein mottling virus RNA. Nucleic Acids Res. 1986 Jul 11;14(13):5417–5430. doi: 10.1093/nar/14.13.5417. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gorbalenya A. E., Donchenko A. P., Koonin E. V., Blinov V. M. N-terminal domains of putative helicases of flavi- and pestiviruses may be serine proteases. Nucleic Acids Res. 1989 May 25;17(10):3889–3897. doi: 10.1093/nar/17.10.3889. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Henikoff S. Unidirectional digestion with exonuclease III creates targeted breakpoints for DNA sequencing. Gene. 1984 Jun;28(3):351–359. doi: 10.1016/0378-1119(84)90153-7. [DOI] [PubMed] [Google Scholar]
  10. Kamer G., Argos P. Primary structural comparison of RNA-dependent polymerases from plant, animal and bacterial viruses. Nucleic Acids Res. 1984 Sep 25;12(18):7269–7282. doi: 10.1093/nar/12.18.7269. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kubo Y., Takeuchi K., Boonmar S., Katayama T., Choo Q. L., Kuo G., Weiner A. J., Bradley D. W., Houghton M., Saito I. A cDNA fragment of hepatitis C virus isolated from an implicated donor of post-transfusion non-A, non-B hepatitis in Japan. Nucleic Acids Res. 1989 Dec 25;17(24):10367–10372. doi: 10.1093/nar/17.24.10367. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kuo G., Choo Q. L., Alter H. J., Gitnick G. L., Redeker A. G., Purcell R. H., Miyamura T., Dienstag J. L., Alter M. J., Stevens C. E. An assay for circulating antibodies to a major etiologic virus of human non-A, non-B hepatitis. Science. 1989 Apr 21;244(4902):362–364. doi: 10.1126/science.2496467. [DOI] [PubMed] [Google Scholar]
  13. Kyte J., Doolittle R. F. A simple method for displaying the hydropathic character of a protein. J Mol Biol. 1982 May 5;157(1):105–132. doi: 10.1016/0022-2836(82)90515-0. [DOI] [PubMed] [Google Scholar]
  14. Mackow E., Makino Y., Zhao B. T., Zhang Y. M., Markoff L., Buckler-White A., Guiler M., Chanock R., Lai C. J. The nucleotide sequence of dengue type 4 virus: analysis of genes coding for nonstructural proteins. Virology. 1987 Aug;159(2):217–228. doi: 10.1016/0042-6822(87)90458-2. [DOI] [PubMed] [Google Scholar]
  15. Maéno M., Kaminaka K., Sugimoto H., Esumi M., Hayashi N., Komatsu K., Abe K., Sekiguchi S., Yano M., Mizuno K. A cDNA clone closely associated with non-A, non-B hepatitis. Nucleic Acids Res. 1990 May 11;18(9):2685–2689. doi: 10.1093/nar/18.9.2685. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Meyers G., Rümenapf T., Thiel H. J. Molecular cloning and nucleotide sequence of the genome of hog cholera virus. Virology. 1989 Aug;171(2):555–567. doi: 10.1016/0042-6822(89)90625-9. [DOI] [PubMed] [Google Scholar]
  17. Miller R. H., Purcell R. H. 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 U S A. 1990 Mar;87(6):2057–2061. doi: 10.1073/pnas.87.6.2057. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Miyamura T., Saito I., Katayama T., Kikuchi S., Tateda A., Houghton M., Choo Q. L., Kuo G. Detection of antibody against antigen expressed by molecularly cloned hepatitis C virus cDNA: application to diagnosis and blood screening for posttransfusion hepatitis. Proc Natl Acad Sci U S A. 1990 Feb;87(3):983–987. doi: 10.1073/pnas.87.3.983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Okamoto H., Okada S., Sugiyama Y., Yotsumoto S., Tanaka T., Yoshizawa H., Tsuda F., Miyakawa Y., Mayumi M. The 5'-terminal sequence of the hepatitis C virus genome. Jpn J Exp Med. 1990 Jun;60(3):167–177. [PubMed] [Google Scholar]
  20. Okayama H., Kawaichi M., Brownstein M., Lee F., Yokota T., Arai K. High-efficiency cloning of full-length cDNA; construction and screening of cDNA expression libraries for mammalian cells. Methods Enzymol. 1987;154:3–28. doi: 10.1016/0076-6879(87)54067-8. [DOI] [PubMed] [Google Scholar]
  21. Perlman D., Halvorson H. O. A putative signal peptidase recognition site and sequence in eukaryotic and prokaryotic signal peptides. J Mol Biol. 1983 Jun 25;167(2):391–409. doi: 10.1016/s0022-2836(83)80341-6. [DOI] [PubMed] [Google Scholar]
  22. Prince A. M., Brotman B., Grady G. F., Kuhns W. J., Hazzi C., Levine R. W., Millian S. J. Long-incubation post-transfusion hepatitis without serological evidence of exposure to hepatitis-B virus. Lancet. 1974 Aug 3;2(7875):241–246. doi: 10.1016/s0140-6736(74)91412-3. [DOI] [PubMed] [Google Scholar]
  23. Rice C. M., Lenches E. M., Eddy S. R., Shin S. J., Sheets R. L., Strauss J. H. Nucleotide sequence of yellow fever virus: implications for flavivirus gene expression and evolution. Science. 1985 Aug 23;229(4715):726–733. doi: 10.1126/science.4023707. [DOI] [PubMed] [Google Scholar]
  24. Schlesinger J. J., Brandriss M. W., Cropp C. B., Monath T. P. Protection against yellow fever in monkeys by immunization with yellow fever virus nonstructural protein NS1. J Virol. 1986 Dec;60(3):1153–1155. doi: 10.1128/jvi.60.3.1153-1155.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Schlesinger J. J., Brandriss M. W., Walsh E. E. Protection of mice against dengue 2 virus encephalitis by immunization with the dengue 2 virus non-structural glycoprotein NS1. J Gen Virol. 1987 Mar;68(Pt 3):853–857. doi: 10.1099/0022-1317-68-3-853. [DOI] [PubMed] [Google Scholar]
  26. Sumiyoshi H., Mori C., Fuke I., Morita K., Kuhara S., Kondou J., Kikuchi Y., Nagamatu H., Igarashi A. Complete nucleotide sequence of the Japanese encephalitis virus genome RNA. Virology. 1987 Dec;161(2):497–510. doi: 10.1016/0042-6822(87)90144-9. [DOI] [PubMed] [Google Scholar]
  27. Westaway E. G., Goodman M. R. Variation in distribution of the three flavivirus-specified glycoproteins detected by immunofluorescence in infected Vero cells. Arch Virol. 1987;94(3-4):215–228. doi: 10.1007/BF01310715. [DOI] [PubMed] [Google Scholar]
  28. Young R. A., Davis R. W. Efficient isolation of genes by using antibody probes. Proc Natl Acad Sci U S A. 1983 Mar;80(5):1194–1198. doi: 10.1073/pnas.80.5.1194. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. von Heijne G. Signal sequences. The limits of variation. J Mol Biol. 1985 Jul 5;184(1):99–105. doi: 10.1016/0022-2836(85)90046-4. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES