Abstract
Hepatitis C virus (HCV), a member of the Flaviviridae family, is an enveloped virus, whose genome is single-stranded, positive-sense RNA of approximately 9.5 kb. The viral genome exhibits a considerable degree of sequence variation, based on which HCV is currently classified into at least 6 clades (previously called genotypes) and more than 60 subtypes (1,2). The HCV genome encodes a polyprotein consisting of about 3010–3033 amino acid residues. A number of studies have shown that this polyprotein is cleaved cotranslationally and posttranslationally into mature viral proteins, which are arranged in the order NH2-C-E1-E2-p7-NS2-NS3-NS4A-NS4B-NS5A-NS5B-COOH (3,4).
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Doi, H., Apichartpiyakul, C., Ohba, K. I., Mizokami, M., and Hotta, H. (1996) Hepatitis C virus (HCV) subtype prevalence in Chiang Mai, Thailand, and identification of novel subtypes of HCV major type 6. J. Clin. Microbiol. 34, 569–574.
Robertson, B., Myers, G., Howard, C., Brettin, T., Bukh, J., Gaschen, B., et al. (1998) Classification, nomenclature, and database development for hepatitis C virus (HCV) and related viruses: proposals for standardization. Arch. Virol. 143, 2493–2503.
Grakoui, A., Wychowski, C., Lin, C., Feinstone, S. M., and Rice, C. M. (1993) Expression and identification of hepatitis C virus polyprotein cleavage products. J. Virol. 67, 1385–1395.
Mizushima, H., Hijikata, M., Asabe, S., Hirota, M., Kimura, K., and Shimotohno, K. (1994) Two hepatitis C virus glycoprotein E2 products with different C termini. J. Virol. 68, 6215–6222.
Alter, H. J., Purcell, R. H., Shih, J. W., Melpolder, J. C., Houghton, M., Choo, Q. L., et al. (1989) Detection of antibody to hepatitis C virus in prospectively followed transfusion recipients with acute and chronic non-A, non-B hepatitis. N. Engl. J. Med. 321, 1494–1500.
Saito, I., Miyamura, T., Ohbayashi, A., Harada, H., Katayama, T., Kikuchi, S., et al. (1990) Hepatitis C virus infection is associated with the development of hepatocellular carcinoma. Proc. Natl. Acad. Sci. USA 87, 6547–6549.
Haruna, Y., Hayashi, N., Hiramatsu, N., Takehara, T., Hagiwara, H., Sasaki, Y., et al. (1993) Detection of hepatitis C virus RNA in liver tissues by an in situ hybridization technique. J. Hepatol. 18, 96–100.
Sakamuro, D., Furukawa, T., and Takegami, T. (1995) Hepatitis C virus nonstructural protein NS3 transforms NIH 3T3 cells. J. Virol. 69, 3893–3896.
Chang, J., Yang, S.-H., Cho, Y.-G., Hwang, S. B., Hahn, Y. S., and Sung, Y. C. (1998) Hepatitis C virus core from two different genotypes has an oncogenic potential but is not sufficient for transforming primary rat embryo fibroblasts in cooperation with the H-ras oncogene. J. Virol. 72, 3060–3065.
Moriya, K., Fujie, H., Shintani, Y., Yotsuyanagi, H., Tsutsumi, T., Ishibashi, K., et al. (1998) The core protein of hepatitis C virus induces hepatocellular carcinoma in transgenic mice. Nature Med. 4, 1065–1067.
Razvi, E. S. and Welsh, R. M. (1995) Apoptosis in viral infections, in Advance in Virus Research (Maramorosch, K., Murphy, F. A., and Shatkin, A. J., eds.), Academic San Diego. pp. 1–60.
Gregory, C. D., Dive, C., Henderson, S., Smith, C. A., Williams, G. T., Gordon, J. et al. (1991) Activation of Epstein-Barr virus latent genes protects human B cells from death by apoptosis. Nature. 349, 612–614.
Henderson, S., Rowe, M., Gregory, C., Croom Carter, D., Wang, F., Longnecker, R., et al. (1991) Induction of bcl-2 expression by Epstein-Barr virus latent membrane protein 1 protects infected B cells from programmed cell death. Cell. 65, 1107–1115.
Rao, L., Debbas, M., Sabbatini, P., Hockenbery, D., Korsmeyer, S., and White, E. (1992) The adenovirus E1A proteins induce apoptosis, which is inhibited by the E1B 19-kDa and Bcl-2 proteins. Proc. Natl. Acad. Sci. USA 89, 7742–7746.
Lechner, M. S. and Laimins, L. A. (1994) Inhibition of p53 DNA binding by human papillomavirus E6 proteins. J. Virol. 68, 4262–4273.
Fujita, T., Ishido, S., Muramatsu, S., Itoh, M., and Hotta, H. (1996) Suppression of actinomycin D-induced apoptosis by the NS3 protein of hepatitis C virus. Biochem. Biophys. Res. Commun. 229, 825–831.
Ishido, S., Muramatsu, S., Fujita, T., Iwanaga, Y., Tong, W. Y., Katayama, Y., et al. (1997) Wild-type, but not mutant-type, p53 enhances nuclear accumulation of the NS3 protein of hepatitis C virus. Biochem. Biophys. Res. Commun. 230, 431–436.
Muramatsu, S., Ishido, S., Fujita, T., Itoh, M., and Hotta, H. (1997) Nuclear localization of the NS3 protein of hepatitis C virus and factors affecting the localization. J. Virol. 71, 4954–4961.
Ishido, S. and Hotta, H. (1998) Complex formation of the Nonstructural protein 3 of hepatitis C virus with the p53 tumor suppressor. FEBS Lett. 438, 258–262.
Martin, S. J., Lennon, S. V., Bonham, A. M., and Cotter, T. G. (1990) Induction of apoptosis (programmed cell death) in human leukemic HL-60 cells by inhibition of RNA or protein synthesis. J. Immunol. 145, 1859–1867.
Tishler, R. B., Calderwood, S. K., Coleman, C. N., and Price, B. D. (1993) Increases in sequence specific DNA binding by p53 following treatment with chemotherapeutic and DNA damaging agents. Cancer Res. 53, 2212–2216.
Price, B. D. and Youmell, M. B. (1996) The phosphatidylinositol 3-kinase inhibitor wortmannin sensitizes murine fibroblasts and human tumor cells to radiation and blocks induction of p53 following DNA damage. Cancer Res. 56, 246–250.
Li, X., Stebbins, B., Hoffman, L., Pratt, G., Rechsteiner, M., and Coffino, P. (1996) The N terminus of antizyme promotes degradation of heterologous proteins. J. Biol. Chem. 271, 4441–4446.
Takamizawa, A., Mori, C., Fuke, I., Manabe, S., Murakami, S., Fujita, J., et al. (1991) Structure and organization of the hepatitis C virus genome isolated from human carriers. J. Virol. 65, 1105–1113.
Kuroki, Y., Shiozawa, S., Yoshihara, R. and Hotta, H. (1993) The contribution of human c-fos DNA to cultured synovial cells: a transfection study. J. Rheumatol. 20, 422–428.
Tamura, T., Aoyama, N., Saya, H., Haga, H., Futami, S., Miyamoto, M., et al. (1995) Induction of Fas-mediated apoptosis in p53-transfected human colon carcinoma cells. Oncogene. 11, 1939–1946.
Miyashita, T. and Reed, J. C. (1995) Tumor suppressor p53 is a direct transcriptional activator of the human bax gene. Cell. 80, 293–299.
Hotta, H., Ross, A. H., Huebner, K., Isobe, M., Wendeborn, S., Chao, M. V., et al. (1988) Molecular cloning and characterization of an antigen associated with early stages of melanoma tumor progression. Cancer Res. 48, 2955–2962.
Fuerst, T. R., Niles, E. G., Studier, F. W., and Moss, B. (1986) Eukaryotic transient-expression system based on recombinant vaccinia virus that synthesizes bacteriophage T7 RNA polymerase. Proc. Natl. Acad. Sci. USA 83, 8122–8126.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2000 Humana Press Inc., Totowa, NJ
About this protocol
Cite this protocol
Ishido, S., Fujita, T., Hotta, H. (2000). Possible Involvement of the NS3 Protein of Hepatitis C Virus in Hepatocarcinogenesis. In: Habib, N.A. (eds) Hepatocellular Carcinoma. Methods in Molecular Medicine™, vol 45. Humana Press. https://doi.org/10.1385/1-59259-079-9:37
Download citation
DOI: https://doi.org/10.1385/1-59259-079-9:37
Publisher Name: Humana Press
Print ISBN: 978-0-89603-785-4
Online ISBN: 978-1-59259-079-7
eBook Packages: Springer Protocols