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 fre quency of persistence and the progression to chronic liver diseases. Recent data suggest that prevalent T helper (Th) 2 immunity as well as weak HCV-s pecific T-cell response is associated with viral persistence. Here, we show ed 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 bo th HCV core-expressing macrophage cell lines and mouse peritoneal macrophag es treated with recombinant core protein. in addition, IL-12 p40 promoter a ctivity was repressed by the presence of HCV core in macrophages stimulated with lipopolysaccharride (LPS) following IFN-gamma treatment, indicating t hat IL-12 production may be downregulated at the transcriptional level. We also found that proliferation of T cells and IFN-gamma , production in mixe d lymphocyte reactions (MLR) with core-expressing cells were inhibited. Tak en together, our results suggest that HCV core protein could play roles in suppressing the induction of Th1 immunity through inhibition of IL-12 and N O production. (C) 2001 Academic Press.