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Journal of Virology, January 2001, p. 772-781, Vol. 75, No. 2
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.2.772-781.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Transcriptional Activation of the Interleukin-2 Promoter by Hepatitis C Virus Core Protein

Anders Bergqvist1,2,* and Charles M. Rice1,dagger

Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri,1 and Department of Medical Biochemistry and Microbiology, Uppsala University Biomedical Centre, Uppsala, Sweden2

Received 17 May 2000/Accepted 2 October 2000

Most patients infected with hepatitis C virus (HCV) become chronic carriers. Viruses that efficiently establish persistent infections must have effective ways of evading host defenses. In the case of HCV, little is known about how chronic infections are established or maintained. Besides hepatocytes, several reports suggest that HCV can infect T and B lymphocytes. Since T cells are essential for viral clearance, direct or indirect effects of HCV on T-cell function could influence the outcome of infection. Given that T-cell growth and differentiation require the cytokine interleukin 2 (IL-2), we asked whether HCV might modulate synthesis of IL-2. Portions of the HCV polyprotein were expressed in Jurkat cells under a variety of conditions. We found that the highly conserved HCV core protein, in combination with other stimuli, was able to dramatically activate transcription from the IL-2 promoter. The carboxy-terminal hydrophobic portion of the core protein was required for this activity. Activation was dependent on nuclear factor of activated T cells (NFAT), occurred in cells deficient in the tyrosine kinase p56lck, and could be blocked by addition of cyclosporin A and by depletion of calcium. These results suggest that the HCV core protein can activate transcription of the IL-2 promoter through the NFAT pathway. This novel activity may have consequences for T-cell development and establishment of persistent infections.

* Corresponding author. Present address: Microbiology and Tumour Biology Centre, Karolinska Institute, Box 280, SE-171 77 Stockholm, Sweden. Phone: 46-8-7287149. Fax: 46-8-331399. E-mail: anders.bergqvist{at}mtc.ki.se.

dagger Present address: Center for the Study of Hepatitis C, Laboratory of Virology and Infectious Diseases, Rockefeller University, New York, N.Y.

Journal of Virology, January 2001, p. 772-781, Vol. 75, No. 2
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.2.772-781.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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