Mutation Pattern of Hepatitis C Virus and Its Application to Therapy

  • Masashi Mizokami
  • Tatsunori Nakano
  • Etsuro Orito
Conference paper


Chronic hepatitis C is a common disease worldwide and is a major cause of chronic liver disease in many countries. However, the current standard therapy of chronic hepatitis C with interferon (IFN) is rather unsatisfactory [1–3]. Therefore, the search for additional therapies needs to be pursued. Molecular evolutionary analysis has been applied to numerous studies of hepatitis C virus (HCV) and has given many informative suggestions. However, it has not yielded helpful information for developing effective antiviral drugs against chronic HCV infection.


Substitution Pattern Mutation Pattern Human Immunodeficiency Virus Replication Full Code Region Nucleotide Substitution Pattern 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Carithers RLJ, Emerson SS (1997) Therapy of hepatitis C: meta-analysis of interferon alfa-2b trials. Hepatology 26(3 suppl 1):83S–88SPubMedCrossRefGoogle Scholar
  2. 2.
    Farrell GC (1997) Therapy of hepatitis C: interferon alfa-nl trials. Hepatology 26(3 suppl 1):96S–100SPubMedCrossRefGoogle Scholar
  3. 3.
    Lee WM (1997) Therapy of hepatitis C: interferon alfa-2a trials. Hepatology 26(3 suppl 1):89S–95SPubMedCrossRefGoogle Scholar
  4. 4.
    Carpenter CC, Fischl MA, Hammer SM, Hirsch MS, Jacobsen DM, Katzenstein DA, Montaner JS, Richman DD, Saag MS, Schooley RT, Thompson MA, Vella S, Yeni PG, Volberding PA (1997) Antiretroviral therapy for HIV infection in 1997. Updated recommendations of the International AIDS Society—USA panel. JAMA 277:1962–1969Google Scholar
  5. 5.
    De Clercq E (1995) Antiviral therapy for human immunodeficiency virus infections. Clin Microbiol Rev 8:200–239PubMedGoogle Scholar
  6. 6.
    Shirasaka T, Kavlick MF, Ueno T, Gao WY, Kojima E, Alcaide ML, Chokekijchai S, Roy BM, Arnold E, Yarchoan R, Mitsuya H (1995) Emergence of human immunodeficiency virus type 1 variants with resistance to multiple dideoxynucleosides in patients receiving therapy with dideoxynucleosides. Proc Natl Acad Sci USA 92:2398–2402PubMedCrossRefGoogle Scholar
  7. 7.
    Shirasaka T, Chokekijchai S, Yamada A, Gosselin G, Imbach JL, Mitsuya H (1995) Comparative analysis of anti-human immunodeficiency virus type 1 activities of dideoxynucleoside analogs in resting and activated peripheral blood mononuclear cells. Antimicrob Agents Chemother 39:2555–2559PubMedGoogle Scholar
  8. 8.
    Moriyama EN, Ina Y, Ikeo K, Shimizu N, Gojobori T (1991) Mutation pattern of human immunodeficiency virus gene. J Mol Evol 32:360–363PubMedCrossRefGoogle Scholar
  9. 9.
    Okamoto H, Okada S, Sugiyama Y, Tanaka T, Sugai Y, Akahane Y, Machida A, Mishiro S, Yoshizawa H, Miyakawa Y, Mayumi M (1990) Detection of hepatitis C virus RNA by a two-stage polymerase chain reaction with two pairs of primers deduced from the 5′-noncoding region. Jpn J Exp Med 60:215–222PubMedGoogle Scholar
  10. 10.
    Ohno O, Mizokami M, Wu RR, Saleh MG, Ohba K, Orito E, Mukaide M, Williams R, Lau JY (1997) New hepatitis C virus (HCV) genotyping system that allows for identification of HCV genotypes la, lb, 2a, 2b, 3a, 3b, 4, 5a, and 6a. J Clin Microbiol 35:201–207PubMedGoogle Scholar
  11. 11.
    Hijikata M, Kato N, Ootsuyama Y, Nakagawa M, Ohkoshi S, Shimotohno K (1991) Hypervariable regions in the putative glycoprotein of hepatitis C virus. Biochem Biophys Res Commun 175:220–228PubMedCrossRefGoogle Scholar
  12. 12.
    Gojobori T, Ishii K, Nei M (1982) Estimation of average number of nucleotide substitutions when the rate of substitution varies with nucleotide. J Mol Evol 18:414–423PubMedCrossRefGoogle Scholar
  13. 13.
    Saitou N, Nei M (1987) The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol Biol Evol 4:406–425PubMedGoogle Scholar
  14. 14.
    Gojobori T, Li WH, Graur D (1982) Patterns of nucleotide substitution in pseudogenes and functional genes. J Mol Evol 18:360–369PubMedCrossRefGoogle Scholar
  15. 15.
    Enomoto N, Kurosaki M, Tanaka Y, Marumo F, Sato C (1994) Fluctuation of hepatitis C virus quasispecies in persistent infection and interferon treatment revealed by single-strand conformation polymorphism analysis. J Gen Virol 75(Pt 6):1361–1369Google Scholar

Copyright information

© Springer-Verlag Tokyo 1999

Authors and Affiliations

  • Masashi Mizokami
    • 1
  • Tatsunori Nakano
    • 1
  • Etsuro Orito
    • 1
  1. 1.Second Department of MedicineNagoya City University Medical SchoolMizuho-ku, NagoyaJapan

Personalised recommendations