Association of HCV mutated proteins and host SNPs in the development of hepatocellular carcinoma
Abstract 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. Highlights There is a strong association between HCV variants within Core, NS4 and NS5A and host SNPs with the HCC pathogenesis. Core and NS5A also trigger the accretion of β-catenin pathway as a common target to contribute viral induced transformation. Single-point mutations, Phe 43 and Leu 106, of HCV NS3 protein, impair its interaction with p53. The A28C polymorphism has been suggested to alter the coil structure of amino acids 8–12 into β-sheet.
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