Vaccine and Infectious Disease Organization, Saskatoon, SK, Canada.
J Viral Hepat. 2011 Oct;18(10):700-13. doi: 10.1111/j.1365-2893.2010.01357.x. Epub 2010 Aug 4.
Hepatitis C virus (HCV) causes a chronic liver infection, which may result in cirrhosis and hepatocellular carcinoma. Impairment of the maturation process in dendritic cells (DCs) may be one of the mechanisms responsible for immune evasion of HCV. The core and NS3 proteins are among the most conserved HCV proteins and play a key role in viral clearance. To evaluate the effects of these proteins on DCs, monocyte-derived immature DCs (iDCs) were transfected with in vitro transcribed (IVT) HCV core or NS3 RNA and treated with maturation factors. Neither core nor NS3 had an inhibitory effect on DC maturation; however, transfection of iDCs with IVT core RNA appeared to result in changes compatible with maturation. To investigate this in more detail, the transcriptional profiles of iDCs transfected with IVT core, NS3 or green fluorescent protein (GFP) RNA were examined using a DC-specific membrane array. Of the 288 genes on the array, 46 genes were distinctively up- or down-regulated by transfection with IVT core RNA in comparison with NS3 or GFP RNA treatments. Forty-two of these genes are involved in DC maturation. The effects of core on maturation of iDCs were confirmed with a significant increase in surface expression of CD83 and HLA-DR, a reduction of phagocytosis, as well as an increase in proliferation and IFN-γ secretion by T cells in a mixed lymphocyte reaction assay. These results show that HCV core does not have an inhibitory effect on human DC maturation, but could be a target for the immune system.
丙型肝炎病毒（HCV）可引起慢性肝脏感染，从而导致肝硬化和肝细胞癌。树突状细胞（DC）成熟过程受损可能是 HCV 免疫逃逸的机制之一。核心蛋白和 NS3 蛋白是 HCV 中最保守的蛋白之一，在病毒清除中发挥关键作用。为了评估这些蛋白对 DC 的影响，用体外转录（IVT）HCV 核心或 NS3 RNA 转染单核细胞来源的未成熟 DC（iDC），并使用成熟因子处理。核心和 NS3 均未对 DC 成熟产生抑制作用；然而，用 IVT 核心 RNA 转染 iDC 似乎会导致与成熟相容的变化。为了更详细地研究这一点，用 DC 特异性膜阵列检测用 IVT 核心、NS3 或绿色荧光蛋白（GFP）RNA 转染的 iDC 的转录谱。在阵列上的 288 个基因中，与 NS3 或 GFP RNA 处理相比，用 IVT 核心 RNA 转染时，有 46 个基因明显上调或下调。其中 42 个基因参与 DC 成熟。用核心蛋白显著增加 CD83 和 HLA-DR 的表面表达、降低吞噬作用、以及在混合淋巴细胞反应试验中增加 T 细胞增殖和 IFN-γ分泌，证实了核心蛋白对 iDC 成熟的影响。这些结果表明，HCV 核心蛋白对人 DC 成熟没有抑制作用，但可能是免疫系统的靶点。
