Search tips
Search criteria 


Logo of jvirolPermissionsJournals.ASM.orgJournalJV ArticleJournal InfoAuthorsReviewers
J Virol. 1995 June; 69(6): 3893–3896.
PMCID: PMC189112

Hepatitis C virus nonstructural protein NS3 transforms NIH 3T3 cells.


Clinical evidence suggests that hepatitis C virus (HCV) is etiologically involved in hepatic cancer and liver cirrhosis. To investigate whether the HCV nonstructural protein NS3 has oncogenic activity, NIH 3T3 cells were transfected with an expression vector containing cDNA for the 5'- or 3'-half sequence of the HCV genome segment encoding NS3. Only cells transfected with the 5'-half cDNA rapidly proliferated, lost contact inhibition, grew anchorage independently in soft agar, and formed tumors in nude mice. PCR analysis confirmed the presence of the 5'-half DNA in the transfectants. These results suggest that the 5' region of the HCV genome segment encoding NS3 is involved in cell transformation.

Full Text

The Full Text of this article is available as a PDF (616K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Bartenschlager R, Ahlborn-Laake L, Mous J, Jacobsen H. Nonstructural protein 3 of the hepatitis C virus encodes a serine-type proteinase required for cleavage at the NS3/4 and NS4/5 junctions. J Virol. 1993 Jul;67(7):3835–3844. [PMC free article] [PubMed]
  • Bazan JF, Fletterick RJ. Detection of a trypsin-like serine protease domain in flaviviruses and pestiviruses. Virology. 1989 Aug;171(2):637–639. [PubMed]
  • Bukh J, Miller RH, Kew MC, Purcell RH. Hepatitis C virus RNA in southern African blacks with hepatocellular carcinoma. Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):1848–1851. [PubMed]
  • Grakoui A, McCourt DW, Wychowski C, Feinstone SM, Rice CM. Characterization of the hepatitis C virus-encoded serine proteinase: determination of proteinase-dependent polyprotein cleavage sites. J Virol. 1993 May;67(5):2832–2843. [PMC free article] [PubMed]
  • Haruna Y, Hayashi N, Hiramatsu N, Takehara T, Hagiwara H, Sasaki Y, Kasahara A, Fusamoto H, Kamada T. Detection of hepatitis C virus RNA in liver tissues by an in situ hybridization technique. J Hepatol. 1993 Apr;18(1):96–100. [PubMed]
  • Hijikata M, Mizushima H, Akagi T, Mori S, Kakiuchi N, Kato N, Tanaka T, Kimura K, Shimotohno K. Two distinct proteinase activities required for the processing of a putative nonstructural precursor protein of hepatitis C virus. J Virol. 1993 Aug;67(8):4665–4675. [PMC free article] [PubMed]
  • Hijikata M, Mizushima H, Tanji Y, Komoda Y, Hirowatari Y, Akagi T, Kato N, Kimura K, Shimotohno K. Proteolytic processing and membrane association of putative nonstructural proteins of hepatitis C virus. Proc Natl Acad Sci U S A. 1993 Nov 15;90(22):10773–10777. [PubMed]
  • Ishihama A, Nagata K. Viral RNA polymerases. CRC Crit Rev Biochem. 1988;23(1):27–76. [PubMed]
  • Kato N, Hijikata M, Ootsuyama Y, Nakagawa M, Ohkoshi S, Sugimura T, Shimotohno K. Molecular cloning of the human hepatitis C virus genome from Japanese patients with non-A, non-B hepatitis. Proc Natl Acad Sci U S A. 1990 Dec;87(24):9524–9528. [PubMed]
  • Tsukiyama-Kohara K, Kohara M, Yamaguchi K, Maki N, Toyoshima A, Miki K, Tanaka S, Hattori N, Nomoto A. A second group of hepatitis C viruses. Virus Genes. 1991 Jul;5(3):243–254. [PubMed]
  • Kumatori A, Tanaka K, Inamura N, Sone S, Ogura T, Matsumoto T, Tachikawa T, Shin S, Ichihara A. Abnormally high expression of proteasomes in human leukemic cells. Proc Natl Acad Sci U S A. 1990 Sep;87(18):7071–7075. [PubMed]
  • Kuo G, Choo QL, Alter HJ, Gitnick GL, Redeker AG, Purcell RH, Miyamura T, Dienstag JL, Alter MJ, Stevens CE, et al. 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. [PubMed]
  • Manabe S, Fuke I, Tanishita O, Kaji C, Gomi Y, Yoshida S, Mori C, Takamizawa A, Yosida I, Okayama H. Production of nonstructural proteins of hepatitis C virus requires a putative viral protease encoded by NS3. Virology. 1994 Feb;198(2):636–644. [PubMed]
  • Mangia A, Vallari DS, Di Bisceglie AM. Use of confirmatory assays for diagnosis of hepatitis C viral infection in patients with hepatocellular carcinoma. J Med Virol. 1994 Jun;43(2):125–128. [PubMed]
  • Rechsteiner M. Natural substrates of the ubiquitin proteolytic pathway. Cell. 1991 Aug 23;66(4):615–618. [PubMed]
  • Rice CM, Lenches EM, Eddy SR, Shin SJ, Sheets RL, Strauss JH. Nucleotide sequence of yellow fever virus: implications for flavivirus gene expression and evolution. Science. 1985 Aug 23;229(4715):726–733. [PubMed]
  • Saito I, Miyamura T, Ohbayashi A, Harada H, Katayama T, Kikuchi S, Watanabe Y, Koi S, Onji M, Ohta Y, et al. Hepatitis C virus infection is associated with the development of hepatocellular carcinoma. Proc Natl Acad Sci U S A. 1990 Sep;87(17):6547–6549. [PubMed]
  • Sherker AH, Marion PL. Hepadnaviruses and hepatocellular carcinoma. Annu Rev Microbiol. 1991;45:475–507. [PubMed]
  • Stanton VP, Jr, Nichols DW, Laudano AP, Cooper GM. Definition of the human raf amino-terminal regulatory region by deletion mutagenesis. Mol Cell Biol. 1989 Feb;9(2):639–647. [PMC free article] [PubMed]
  • Suzich JA, Tamura JK, Palmer-Hill F, Warrener P, Grakoui A, Rice CM, Feinstone SM, Collett MS. Hepatitis C virus NS3 protein polynucleotide-stimulated nucleoside triphosphatase and comparison with the related pestivirus and flavivirus enzymes. J Virol. 1993 Oct;67(10):6152–6158. [PMC free article] [PubMed]
  • Takada S, Koike K. X protein of hepatitis B virus resembles a serine protease inhibitor. Jpn J Cancer Res. 1990 Dec;81(12):1191–1194. [PubMed]
  • Takamizawa A, Mori C, Fuke I, Manabe S, Murakami S, Fujita J, Onishi E, Andoh T, Yoshida I, Okayama H. Structure and organization of the hepatitis C virus genome isolated from human carriers. J Virol. 1991 Mar;65(3):1105–1113. [PMC free article] [PubMed]
  • Takegami T, Sakamuro D, Furukawa T. Japanese encephalitis virus nonstructural protein NS3 has RNA binding and ATPase activities. Virus Genes. 1995 Jan;9(2):105–112. [PubMed]
  • Tomei L, Failla C, Santolini E, De Francesco R, La Monica N. NS3 is a serine protease required for processing of hepatitis C virus polyprotein. J Virol. 1993 Jul;67(7):4017–4026. [PMC free article] [PubMed]
  • Tsukuma H, Hiyama T, Tanaka S, Nakao M, Yabuuchi T, Kitamura T, Nakanishi K, Fujimoto I, Inoue A, Yamazaki H, et al. Risk factors for hepatocellular carcinoma among patients with chronic liver disease. N Engl J Med. 1993 Jun 24;328(25):1797–1801. [PubMed]
  • Unsal H, Yakicier C, Marçais C, Kew M, Volkmann M, Zentgraf H, Isselbacher KJ, Ozturk M. Genetic heterogeneity of hepatocellular carcinoma. Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):822–826. [PubMed]

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