Schulze zur Wiesch J, Schmitz H, Borowski E, Borowski P
Partners AIDS Research Center, Massachusetts General Hospital, Charlestown, Massachusetts, USA.
Arch Virol. 2003 Jul;148(7):1247-67. doi: 10.1007/s00705-003-0115-8.
Chronic infection with Hepatitis C virus (HCV) often results in cirrhosis and enhances the probability of developing hepatocellular carcinoma (HCC). The underlying mechanisms that lead to malignant transformation of infected cells, however, remain unclear. Observations made with isolated HCV antigens and/or with HCV subgenomic replicon systems demonstrated that the products encoded in the HCV genome interfere with and disturb intracellular signal transduction, often by phosphorylation of cellular proteins. Moreover, some of the HCV-encoded proteins seem to serve as substrates for host cell protein kinases. These phosphorylations affect the biological functions of the antigens. In many cases it could be demonstrated that only short stretches of the linear sequence of the viral or cellular proteins are involved and play a crucial role for these phosphorylation events. The identification of these small polypeptide elements and the subsequent development of strategies to inhibit protein-protein interactions involving them may be the first step towards reducing the chronicity and/or of the carcinogenicity of the virus. This review summarizes current knowledge of intracellular phosphorylation processes that are affected by HCV.
丙型肝炎病毒（HCV）的慢性感染常导致肝硬化，并增加肝细胞癌（HCC）的发生几率。然而，导致受感染细胞发生恶性转化的潜在机制仍不清楚。对分离出的HCV抗原和/或HCV亚基因组复制子系统的观察表明，HCV基因组编码的产物通常通过细胞蛋白的磷酸化来干扰和扰乱细胞内信号转导。此外，一些HCV编码的蛋白似乎可作为宿主细胞蛋白激酶的底物。这些磷酸化作用会影响抗原的生物学功能。在许多情况下，可以证明只有病毒或细胞蛋白线性序列的短片段参与其中，并在这些磷酸化事件中起关键作用。鉴定这些小的多肽元件以及随后制定策略抑制涉及它们的蛋白质-蛋白质相互作用，可能是降低病毒慢性感染和/或致癌性的第一步。本综述总结了目前关于受HCV影响的细胞内磷酸化过程的知识。
