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Journal of Virology, December 1998, p. 9722-9728, Vol. 72, No. 12
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Ectopic Expression of Hepatitis C Virus Core Protein Differentially Regulates Nuclear Transcription Factors

Anju Shrivastava,1 Sunil K. Manna,1 Ranjit Ray,2,* and Bharat B. Aggarwal1

Cytokine Research Laboratory, Department of Molecular Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030,1 and Division of Infectious Diseases and Immunology, Department of Internal Medicine, Saint Louis University, St. Louis, Missouri 631102

Received 28 July 1998/Accepted 18 September 1998

The putative core protein of hepatitis C virus (HCV) regulates cellular growth and a number of cellular promoters. To further understand its effect, we investigated the role of the core protein in the endogenous regulation of two distinct transcription factors, nuclear factor-kappa B (NF-kappa B) and activating protein-1 (AP-1), and the related mitogen-activated protein kinase kinase (MAPKK) and c-Jun N-terminal kinase (JNK). Stable cell transfectants expressing the HCV core protein suppressed tumor necrosis factor (TNF)-induced NF-kappa B activation. Supershift analysis revealed that NF-kappa B consists of p50 and p65 subunits. This correlated with inhibition of the degradation of Ikappa Balpha , the inhibitory subunit of NF-kappa B. The effect was not specific to TNF, as suppression in core protein-expressing cells was also observed in response to a number of other inflammatory agents known to activate NF-kappa B. In contrast to the effect on NF-kappa B, the HCV core protein constitutively activated AP-1, which correlated with the activation of JNK and MAPKK, which are known to regulate AP-1. These observations indicated that the core protein targets transcription factors known to be involved in the regulation of inflammatory responses and the immune system.

* Corresponding author. Mailing address: Saint Louis University, School of Medicine, 3635 Vista Ave., FDT 8N, St. Louis, MO 63110. Phone: (314) 577-8648. Fax: (314) 771-3816. E-mail: rayr{at}wpogate.slu.edu.

Journal of Virology, December 1998, p. 9722-9728, Vol. 72, No. 12
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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