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Beirne Carter Center for Immunology Research and
Department of Pathology, University of Virginia, Charlottesville, VA 22908
Hepatitis C virus (HCV) is a major human pathogen causing mild to
severe liver disease worldwide. This positive strand RNA virus is
remarkably efficient at establishing chronic infections. Although a
high rate of genetic variability may facilitate viral escape and
persistence in the face of Ag-specific immune responses, HCV may also
encode proteins that facilitate evasion of immunological surveillance.
To address the latter possibility, we examined the influence of
specific HCV gene products on the host immune response to vaccinia
virus in a murine model. Various vaccinia/HCV recombinants expressing
different regions of the HCV polyprotein were used for i.p. inoculation
of BALB/c mice. Surprisingly, a recombinant expressing the N-terminal
half of the polyprotein (including the structural proteins, p7, NS2,
and a portion of NS3; vHCV-S) led to a dose-dependent increase in
mortality. Increased mortality was not observed for a recombinant
expressing the majority of the nonstructural region or for a negative
control virus expressing the ß-galactosidase protein. Examination of
T cell responses in these mice revealed a marked suppression of
vaccinia-specific CTL responses and a depressed production of IFN-
and IL-2. By using a series of vaccinia/HCV recombinants, we found that
the HCV core protein was sufficient for immunosuppression, prolonged
viremia, and increased mortality. These results suggest that the HCV
core protein plays an important role in the establishment and
maintenance of HCV infection by suppressing host immune responses, in
particular the generation of virus-specific CTLs.
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S. Bichr, R. Rende-Fournier, G. Vona, A.-M. Yamamoto, E. Depla, G. Maertens, and C. Brechot Detection of neutralizing antibodies to hepatitis C virus using a biliary cell infection model J. Gen. Virol., June 1, 2002; 83(7): 1673 - 1678. [Abstract] [Full Text] [PDF]
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J. Sun, F. Bodola, X. Fan, H. Irshad, L. Soong, S. M. Lemon, and T.-S. Chan Hepatitis C Virus Core and Envelope Proteins Do Not Suppress the Host's Ability To Clear a Hepatic Viral Infection J. Virol., December 15, 2001; 75(24): 11992 - 11998. [Abstract] [Full Text] [PDF]
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Z. Q. Yao, D. T. Nguyen, A. I. Hiotellis, and Y. S. Hahn Hepatitis C Virus Core Protein Inhibits Human T Lymphocyte Responses by a Complement-Dependent Regulatory Pathway J. Immunol., November 1, 2001; 167(9): 5264 - 5272. [Abstract] [Full Text] [PDF]
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A. Bergqvist and C. M. Rice Transcriptional Activation of the Interleukin-2 Promoter by Hepatitis C Virus Core Protein J. Virol., January 15, 2001; 75(2): 772 - 781. [Abstract] [Full Text]
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T.-H. Wang, R. C. A. Rijnbrand, and S. M. Lemon Core Protein-Coding Sequence, but Not Core Protein, Modulates the Efficiency of Cap-Independent Translation Directed by the Internal Ribosome Entry Site of Hepatitis C Virus J. Virol., December 1, 2000; 74(23): 11347 - 11358. [Abstract] [Full Text]
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 T. J. Liang, B. Rehermann, L. B. Seeff, and J. H. Hoofnagle Pathogenesis, Natural History, Treatment, and Prevention of Hepatitis C Ann Intern Med, February 15, 2000; 132(4): 296 - 305. [Abstract] [Full Text] [PDF]
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 T. Arichi, T. Saito, M. E. Major, I. M. Belyakov, M. Shirai, V. H. Engelhard, S. M. Feinstone, and J. A. Berzofsky Prophylactic DNA vaccine for hepatitis C virus (HCV) infection: HCV-specific cytotoxic T lymphocyte induction and protection from HCV-recombinant vaccinia infection in an HLA-A2.1 transgenic mouse model PNAS, January 4, 2000; 97(1): 297 - 302. [Abstract] [Full Text] [PDF]
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T. Shimoike, S. Mimori, H. Tani, Y. Matsuura, and T. Miyamura Interaction of Hepatitis C Virus Core Protein with Viral Sense RNA and Suppression of Its Translation J. Virol., December 1, 1999; 73(12): 9718 - 9725. [Abstract] [Full Text]
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