King Fahd Medical Research Center, King Abdulaziz University, PO Box 80216, Jeddah 21589, Saudi Arabia.
Special Infectious Agents Unit, King Fahd Medical Research Center, King Abdulaziz University, PO Box 80216, Jeddah 21589, Saudi Arabia.
Infect Genet Evol. 2018 Jun;60:160-172. doi: 10.1016/j.meegid.2018.02.034. Epub 2018 Mar 1.
Hepatitis C virus plays a significant role in the development of hepatocellular carcinoma (HCC) globally. The pathogenic mechanisms of hepatocellular carcinoma with HCV infection are generally linked with inflammation, cytokines, fibrosis, cellular signaling pathways, and liver cell proliferation modulating pathways. HCV encoded proteins (Core, NS3, NS4, NS5A) interact with a broad range of hepatocytes derived factors to modulate an array of activities such as cell signaling, DNA repair, transcription and translational regulation, cell propagation, apoptosis, membrane topology. These four viral proteins are also implicated to show a strong conversion potential in tissue culture. Furthermore, Core and NS5A also trigger the accretion of the β-catenin pathway as a common target to contribute viral induced transformation. There is a strong association between HCV variants within Core, NS4, and NS5A and host single nucleotide polymorphisms (SNPs) with the HCC pathogenesis. Identification of such viral mutants and host SNPs is very critical to determine the risk of HCC and response to antiviral therapy. In this review, we highlight the association of key variants, mutated proteins, and host SNPs in development of HCV induced HCC. How such viral mutants may modulate the interaction with cellular host machinery is also discussed.
丙型肝炎病毒在全球范围内对肝细胞癌（HCC）的发展起着重要作用。丙型肝炎病毒感染导致肝细胞癌的发病机制通常与炎症、细胞因子、纤维化、细胞信号通路和肝细胞增殖调节途径有关。丙型肝炎病毒编码的蛋白（核心、NS3、NS4、NS5A）与广泛的肝细胞衍生因子相互作用，调节一系列活性，如细胞信号转导、DNA 修复、转录和翻译调控、细胞增殖、细胞凋亡、膜拓扑结构。这四种病毒蛋白也被认为在组织培养中具有很强的转化潜能。此外，核心和 NS5A 还触发β-连环蛋白途径的积累，作为促进病毒诱导转化的共同靶点。HCV 变异体在核心、NS4 和 NS5A 内与 HCC 发病机制中的宿主单核苷酸多态性（SNP）之间存在很强的关联。鉴定这些病毒突变体和宿主 SNPs 对于确定 HCC 的风险和对抗病毒治疗的反应非常重要。在这篇综述中，我们强调了关键变异体、突变蛋白和宿主 SNP 在丙型肝炎病毒诱导的 HCC 发展中的关联。还讨论了这些病毒突变体如何调节与细胞宿主机制的相互作用。
