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Journal of Virology, November 2007, p. 12375-12381, Vol. 81, No. 22
0022-538X/07/$08.00+0     doi:10.1128/JVI.01695-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Hepatitis C Virus Infection Induces the Beta Interferon Signaling Pathway in Immortalized Human Hepatocytes{triangledown}

Tatsuo Kanda,1 Robert Steele,1 Ranjit Ray,2,3 and Ratna B. Ray1,2,3*

Departments of Pathology,1 Internal Medicine,2 Liver Center, Saint Louis University, St. Louis, Missouri 631103

Received 5 August 2007/ Accepted 28 August 2007

Beta interferon (IFN-ß) expression is triggered by double-stranded RNA, a common intermediate in the replication of many viruses including hepatitis C virus (HCV). The recent development of cell culture-grown HCV allowed us to analyze the IFN signaling pathway following virus infection. In this study, we have examined the IFN-ß signaling pathway following infection of immortalized human hepatocytes (IHH) with HCV genotype 1a (clone H77) or 2a (clone JFH1). We observed that IHH possesses a functional Toll-like receptor 3 pathway. HCV infection in IHH enhanced IFN-ß and IFN-stimulated gene 56 (ISG56) promoter activities; however, poly(I-C)-induced IFN-ß and ISG56 expression levels were modestly inhibited upon HCV infection. IHH infected with HCV (genotype 1a or 2a) exhibited various levels of translocation of IRF-3 into the nucleus. The upregulation of endogenous IFN-ß and 2',5'-oligoadenylate synthetase 1 mRNA expression was also observed in HCV-infected IHH. Subsequent studies suggested that HCV infection in IHH enhanced STAT1 and ISG56 protein expression. A functional antiviral response of HCV-infected IHH was observed by the growth-inhibitory role in vesicular stomatitis virus. Together, our results suggested that HCV infection in IHH induces the IFN signaling pathway, which corroborates observations from natural HCV infection in humans.


* Corresponding author. Mailing address: Department of Pathology, Saint Louis University, 1402 S. Grand Blvd., St. Louis, MO 63104. Phone: (314) 577-8331. Fax: (314) 771-3816. E-mail: rayrb{at}slu.edu

{triangledown} Published ahead of print on 5 September 2007.


Journal of Virology, November 2007, p. 12375-12381, Vol. 81, No. 22
0022-538X/07/$08.00+0     doi:10.1128/JVI.01695-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.




This article has been cited by other articles:

  • Ait-Goughoulte, M., Kanda, T., Meyer, K., Ryerse, J. S., Ray, R. B., Ray, R. (2008). Hepatitis C Virus Genotype 1a Growth and Induction of Autophagy. J. Virol. 82: 2241-2249 [Abstract] [Full Text]