Hepatitis C Virus Core Protein Inhibits Interleukin 12 and Nitric Oxide Production from Activated Macrophages

A characteristic feature of hepatitis C virus (HCV) infection is a high frequency of persistence and the progression to chronic liver diseases. Recent data suggest that prevalent T helper (Th) 2 immunity as well as weak HCV-specific T-cell response is associated with viral persistence. Here, we show...

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Bibliographic Details
Published in:Virology (New York, N.Y.) N.Y.), 2001-01, Vol.279 (1), p.271-279
Main Authors: Lee, Chu Hee, Choi, Yo Han, Yang, Se-Hwan, Lee, Chang Woo, Ha, Sang Jun, Sung, Young Chul
Format: Article
Language:English
Subjects:
Animals
Cell Line
g-Interferon
Hepacivirus - physiology
hepatitis C virus
Humans
Interferon-gamma - biosynthesis
Interleukin-12 - biosynthesis
Lymphocyte Culture Test, Mixed
Macrophage Activation
Macrophages - immunology
Macrophages - metabolism
Macrophages - virology
Macrophages, Peritoneal - virology
Mice
Mice, Transgenic
Monocytes
nitric oxide
Nitric Oxide - biosynthesis
Recombinant Proteins - pharmacology
Transcription, Genetic
Tumor Necrosis Factor-alpha - biosynthesis
Viral Core Proteins - genetics
Viral Core Proteins - metabolism
Viral Core Proteins - pharmacology
Viral Core Proteins - physiology
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Summary:A characteristic feature of hepatitis C virus (HCV) infection is a high frequency of persistence and the progression to chronic liver diseases. Recent data suggest that prevalent T helper (Th) 2 immunity as well as weak HCV-specific T-cell response is associated with viral persistence. Here, we showed that the production of interleukin 12 (IL-12) and nitric oxide (NO) that is critical for the induction of Th1 and innate immunity, but not that of tumor necrosis factor α (TNF-α), was significantly suppressed in both HCV core-expressing macrophage cell lines and mouse peritoneal macrophages treated with recombinant core protein. In addition, IL-12 p40 promoter activity was repressed by the presence of HCV core in macrophages stimulated with lipopolysaccharride (LPS) following IFN-γ treatment, indicating that IL-12 production may be downregulated at the transcriptional level. We also found that proliferation of T cells and IFN-γ production in mixed lymphocyte reactions (MLR) with core-expressing cells were inhibited. Taken together, our results suggest that HCV core protein could play roles in suppressing the induction of Th1 immunity through inhibition of IL-12 and NO production.
ISSN:0042-6822
1096-0341
DOI:10.1006/viro.2000.0694