Lee C H, Choi Y H, Yang S H, Lee C W, Ha S J, Sung Y C
Department of Life Science, Pohang University of Science and Technology, San 31, Hyoja-dong, Pohang, 790-784, Korea.
Virology. 2001 Jan 5;279(1):271-9. doi: 10.1006/viro.2000.0694.
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.
丙型肝炎病毒（HCV）感染的一个特征是持续感染的高频率以及向慢性肝病的进展。最近的数据表明，普遍存在的辅助性T细胞（Th）2免疫以及较弱的HCV特异性T细胞反应与病毒持续存在有关。在此，我们发现，在表达HCV核心蛋白的巨噬细胞系和用重组核心蛋白处理的小鼠腹腔巨噬细胞中，对Th1和固有免疫诱导至关重要的白细胞介素12（IL-12）和一氧化氮（NO）的产生受到显著抑制，但肿瘤坏死因子α（TNF-α）的产生未受抑制。此外，在用干扰素-γ处理后再用脂多糖（LPS）刺激的巨噬细胞中，HCV核心蛋白的存在会抑制IL-12 p40启动子活性，这表明IL-12的产生可能在转录水平上被下调。我们还发现，在与表达核心蛋白的细胞进行的混合淋巴细胞反应（MLR）中，T细胞的增殖和IFN-γ的产生受到抑制。综上所述，我们的结果表明，HCV核心蛋白可能通过抑制IL-12和NO的产生在抑制Th1免疫诱导中发挥作用。
