Functional and Applied Genomics Laboratory, National Center of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan.
Infect Genet Evol. 2011 Apr;11(3):543-56. doi: 10.1016/j.meegid.2011.01.017. Epub 2011 Feb 1.
Hepatitis C virus (HCV), a RNA virus belonging to the family Flaviviridae, has been considered to be a significant risk factor in HCV induced liver diseases and development of hepatocellular carcinoma (HCC). Current combination treatment of pegylated interferon-α (PEG-IFN-α) and ribavirin has shown limited efficiency, poor tolerability and significant expense mainly depending upon the HCV genotype. HCV has been divided into six genotypes and 52 subtypes present all over the world. The genetic diversity is more than 30% in different genotypes and 20% in subtypes. It has been suggested that different genotypes do vary in their infectivity and pathogenicity due to the variations in amino acid sequence, thereby influencing the rate of disease progression, severity to cirrhosis and the risk of HCC. HCV Core protein has multifunctional activities in regulation of cells growth and host genes expression essential for infectivity including apoptosis, HCV associated steatosis, immune cell functions, cell transformation, signal transduction and transcriptional regulation. Recent studies have shown variable responses for IFN-ribavirin combination therapy, steatosis, insulin resistance and HCC due to amino acid substitutions in HCV Core region of different genotypes. In the present review, we emphasize on the pathogenicity cause by HCV Core and effect of amino acid sequence variation in disease progression and HCV life cycle.
丙型肝炎病毒（HCV），一种属于黄病毒科的 RNA 病毒，被认为是丙型肝炎病毒引起的肝脏疾病和肝细胞癌（HCC）发展的重要危险因素。目前聚乙二醇干扰素-α（PEG-IFN-α）和利巴韦林的联合治疗显示出有限的疗效、较差的耐受性和显著的费用，这主要取决于 HCV 基因型。HCV 已分为 6 个基因型和 52 个亚型，分布于世界各地。不同基因型之间的遗传多样性超过 30%，亚型之间的遗传多样性超过 20%。由于氨基酸序列的变化，不同基因型的 HCV 在感染性和致病性上确实存在差异，从而影响疾病进展速度、肝硬化严重程度和 HCC 风险。HCV 核心蛋白在调节细胞生长和宿主基因表达方面具有多种功能，这些功能对于感染性至关重要，包括细胞凋亡、HCV 相关脂肪变性、免疫细胞功能、细胞转化、信号转导和转录调控。最近的研究表明，由于不同基因型 HCV 核心区的氨基酸取代，干扰素-利巴韦林联合治疗、脂肪变性、胰岛素抵抗和 HCC 的反应存在差异。在本综述中，我们强调了 HCV 核心蛋白的致病性以及氨基酸序列变异对疾病进展和 HCV 生命周期的影响。
