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 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 alpha (TNF-alpha), 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-gamma treatment, indicating that IL-12 production may be downregulated at the transcriptional level. We also found that proliferation of T cells and IFN-gamma 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.
Lee
C H
CH
Department of Life Science, Pohang University of Science and Technology, San 31, Hyoja-dong, Pohang, 790-784, Korea.
Choi
Y H
YH
Yang
S H
SH
Lee
C W
CW
Ha
S J
SJ
Sung
Y C
YC
D000818:Animals; D002460:Cell Line; D016174:Hepacivirus / Q000502:physiology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis*; D007959:Lymphocyte Culture Test, Mixed; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology / Q000378:metabolism* / Q000821:virology*; D017737:Macrophages, Peritoneal / Q000821:virology; D051379:Mice; D008822:Mice, Transgenic; D009000:Monocytes; D009569:Nitric Oxide / Q000096:biosynthesis*; D011994:Recombinant Proteins / Q000494:pharmacology; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014758:Viral Core Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*
D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus; D018664:Interleukin-12; D009569:Nitric Oxide; D007371:Interferon-gamma