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

• DOI: 10.1006/viro.2000.0694
• Publication Date: 2002-09-19T13:00:16Z
• Authors: Chu Hee Lee; Yo Han Choi; Se-Hwan Yang; Chang Woo Lee; Sang Jun Ha; Young Chul Sung
• Keywords: INTERFERON; 0301 basic medicine; 570; Transcription, Genetic; 610; Mice, Transgenic; Hepacivirus; BLOOD MONONUCLEAR-CELLS; Nitric Oxide; DENDRITIC CELLS; Monocytes; Cell Line; Interferon-gamma; Mice; 03 medical and health sciences; Virology; INFECTION; KINASE; IMMUNE-RESPONSE; Animals; Humans; HEMATOPOIETIC-CELLS; IN-VIVO; Tumor Necrosis Factor-alpha; IL-12 PRODUCTION; Macrophages; Viral Core Proteins; T-HELPER CELLS; Macrophage Activation; Interleukin-12; Recombinant Proteins; 3. Good health; Macrophages, Peritoneal; Lymphocyte Culture Test, Mixed

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.