1887

Abstract

The establishment of clonal infection of hepatitis C virus (HCV) in a small-animal model is important for the analysis of HCV virology. A previous study developed models of molecularly cloned genotype 1a and 2a HCV infection using human hepatocyte-transplanted chimeric mice. This study developed a new model of molecularly cloned genotype 1b HCV infection. A full-length genotype 1b HCV genome, HCV-KT9, was cloned from a serum sample from a patient with severe acute hepatitis. The chimeric mice were inoculated intrahepatically with -transcribed HCV-KT9 RNA. Inoculated mice developed viraemia at 2 weeks post-infection, and this persisted for more than 6 weeks. Passage experiments indicated that the sera of these mice contained infectious HCV. Interestingly, a similar clone, HCV-KT1, in which the poly(U/UC) tract was 29 nt shorter than in HCV-KT9, showed poorer infectivity and replication ability. An study showed that no virus was produced in the culture medium from HCV-KT9-transfected cells. In conclusion, this study developed a genetically engineered genotype 1b HCV-infected mouse. This mouse model will be useful for the study of HCV virology, particularly the mechanism underlying the variable resistance of HCV genotypes to interferon therapy.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.83658-0
2008-09-01
2024-03-29
Loading full text...

Full text loading...

/deliver/fulltext/jgv/89/9/2108.html?itemId=/content/journal/jgv/10.1099/vir.0.83658-0&mimeType=html&fmt=ahah

References

  1. Beard M. R., Abell G., Honda M., Carroll A., Gartland M., Clarke B., Suzuki K., Lanford R., Sangar D. V., Lemon S. M. 1999; An infectious molecular clone of a Japanese genotype 1b hepatitis C virus. Hepatology 30:316–324 [CrossRef]
    [Google Scholar]
  2. Bukh J., Pietschmann T., Lohmann V., Krieger N., Faulk K., Engle R. E., Govindarajan S., Shapiro M., St Claire M. other authors 2002; Mutations that permit efficient replication of hepatitis C virus RNA in Huh-7 cells prevent productive replication in chimpanzees. Proc Natl Acad Sci U S A 99:14416–14421 [CrossRef]
    [Google Scholar]
  3. Enomoto N., Sakuma I., Asahina Y., Kurosaki M., Murakami T., Yamamoto C., Ogura Y., Izumi N., Marumo F. other authors 1996; Mutations in the nonstructural protein 5A gene and response to interferon in patients with chronic hepatitis C virus 1b infection. N Engl J Med 334:77–81 [CrossRef]
    [Google Scholar]
  4. Friebe P., Bartenschlager R. 2002; Genetic analysis of sequences in the 3′ nontranslated region of hepatitis C virus that are important for RNA replication. J Virol 76:5326–5338 [CrossRef]
    [Google Scholar]
  5. Fried M. W., Shiffman M. L., Reddy K. R., Smith C., Marinos G., Goncales F. L. Jr, Haussinger D., Diago M., Carosi G. other authors 2002; Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med 347:975–982 [CrossRef]
    [Google Scholar]
  6. Gale M. J. Jr, Korth M. J., Tang N. M., Tan S. L., Hopkins D. A., Dever T. E., Polyak S. J., Gretch D. R., Katze M. G. 1997; Evidence that hepatitis C virus resistance to interferon is mediated through repression of the PKR protein kinase by the nonstructural 5A protein. Virology 230:217–227 [CrossRef]
    [Google Scholar]
  7. 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 18:414–423 [CrossRef]
    [Google Scholar]
  8. Heller T., Saito S., Auerbach J., Williams T., Moreen T. R., Jazwinski A., Cruz B., Jeurkar N., Sapp R. other authors 2005; An in vitro model of hepatitis C virion production. Proc Natl Acad Sci U S A 102:2579–2583 [CrossRef]
    [Google Scholar]
  9. Hiraga N., Imamura M., Tsuge M., Noguchi C., Takahashi S., Iwao E., Fujimoto Y., Abe H., Maekawa T. other authors 2007; Infection of human hepatocyte chimeric mouse with genetically engineered hepatitis C virus and its susceptibility to interferon. FEBS Lett 581:1983–1987 [CrossRef]
    [Google Scholar]
  10. Kato T., Matsumura T., Heller T., Saito S., Sapp R. K., Murthy K., Wakita T., Liang T. J. 2007; Production of infectious hepatitis C virus of various genotypes in cell cultures. J Virol 81:4405–4411 [CrossRef]
    [Google Scholar]
  11. Kneteman N. M., Weiner A. J., O'Connell J., Collett M., Gao T., Aukerman L., Kovelsky R., Ni Z. J., Zhu Q. other authors 2006; Anti-HCV therapies in chimeric scid-Alb/uPA mice parallel outcomes in human clinical application. Hepatology 43:1346–1353 [CrossRef]
    [Google Scholar]
  12. Lindenbach B. D., Meuleman P., Ploss A., Vanwolleghem T., Syder A. J., McKeating J. A., Lanford R. E., Feinstone S. M., Major M. E. other authors 2006; Cell culture-grown hepatitis C virus is infectious in vivo and can be recultured in vitro. Proc Natl Acad Sci U S A 103:3805–3809 [CrossRef]
    [Google Scholar]
  13. Lohmann V., Korner F., Koch J., Herian U., Theilmann L., Bartenschlager R. 1999; Replication of subgenomic hepatitis C virus RNAs in a hepatoma cell line. Science 285:110–113 [CrossRef]
    [Google Scholar]
  14. Mercer D. F., Schiller D. E., Elliott J. F., Douglas D. N., Hao C., Rinfret A., Addison W. R., Fischer K. P., Churchill T. A. other authors 2001; Hepatitis C virus replication in mice with chimeric human livers. Nat Med 7:927–933 [CrossRef]
    [Google Scholar]
  15. Okamoto H., Kojima M., Okada S., Yoshizawa H., Iizuka H., Tanaka T., Muchmore E. E., Peterson D. A., Ito Y. other authors 1992; Genetic drift of hepatitis C virus during an 8.2-year infection in a chimpanzee: variability and stability. Virology 190:894–899 [CrossRef]
    [Google Scholar]
  16. Saitou N., Nei M. 1987; The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol Biol Evol 4:406–425
    [Google Scholar]
  17. Simmonds P., Holmes E. C., Cha T. A., Chan S. W., McOmish F., Irvine B., Beall E., Yap P. L., Kolberg J. other authors 1993; Classification of hepatitis C virus into six major genotypes and a series of subtypes by phylogenetic analysis of the NS-5 region. J Gen Virol 74:2391–2399 [CrossRef]
    [Google Scholar]
  18. Takamizawa A., Mori C., Fuke I., Manabe S., Murakami S., Fujita J., Onishi E., Andoh T., Yoshida I. other authors 1991; Structure and organization of the hepatitis C virus genome isolated from human carriers. J Virol 65:1105–1113
    [Google Scholar]
  19. Tateno C., Yoshizane Y., Saito N., Kataoka M., Utoh R., Yamasaki C., Tachibana A., Soeno Y., Asahina K. other authors 2004; Near completely humanized liver in mice shows human-type metabolic responses to drugs. Am J Pathol 165:901–912 [CrossRef]
    [Google Scholar]
  20. Thomson M., Nascimbeni M., Gonzales S., Murthy K. K., Rehermann B., Liang T. J. 2001; Emergence of a distinct pattern of viral mutations in chimpanzees infected with a homogeneous inoculum of hepatitis C virus. Gastroenterology 121:1226–1233 [CrossRef]
    [Google Scholar]
  21. Tsuge M., Hiraga N., Takaishi H., Noguchi C., Oga H., Imamura M., Takahashi S., Iwao E., Fujimoto Y. other authors 2005; Infection of human hepatocyte chimeric mouse with genetically engineered hepatitis B virus. Hepatology 42:1046–1054 [CrossRef]
    [Google Scholar]
  22. Wakita T., Pietschmann T., Kato T., Date T., Miyamoto M., Zhao Z., Murthy K., Habermann A., Krausslich H. G. other authors 2005; Production of infectious hepatitis C virus in tissue culture from a cloned viral genome. Nat Med 11:791–796 [CrossRef]
    [Google Scholar]
  23. Yi M., Lemon S. M. 2003; 3′ Nontranslated RNA signals required for replication of hepatitis C virus RNA. J Virol 77:3557–3568 [CrossRef]
    [Google Scholar]
  24. You S., Rice C. M. 2008; 3′ RNA elements in hepatitis C virus replication: kissing partners and long poly(U. J Virol 82:184–195 [CrossRef]
    [Google Scholar]
  25. Zhong J., Gastaminza P., Cheng G., Kapadia S., Kato T., Burton D. R., Wieland S. F., Uprichard S. L., Wakita T. other authors 2005; Robust hepatitis C virus infection in vitro . Proc Natl Acad Sci U S A 102:9294–9299 [CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.83658-0
Loading
/content/journal/jgv/10.1099/vir.0.83658-0
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error