HCV-Host Interactions: Interplay Part 2: Host Related Determinants and Intracellular Signaling

Abstract

The progression of acute HCV infection to chronic disease and subsequent extrahepatic comorbidities involve both viruses and host cellular proteins interactions as well as insurrection or subjection of cell signaling and metabolic pathways in infected cells. This interaction between host-specific factors and the hepatitis C genome also weakens or impairs other physiological or metabolic regulatory roles of the hepatocytes. Several host cell proteins promote hepatitis C infection through binding to HCV nonstructural proteins (e.g., PPP2R5D). Some studies also found cytokine (e.g., IL-10, IL-6, TNF-α, and TGF-β1) gene polymorphisms to be highly associated with chronic hepatitis C (CHC) infection progression, whereas, polymorphism in some host genes (e.g., PNPLA3, ADAR-1, and IFIH1) are found to be actively involved in the induction of advanced liver fibrosis in patients co-infected with HIV-1/HCV. Host lipid metabolism reprogramming through host lipid regulators (e.g., ANGPTL-3 and 4) is also considered essential for CHC progression to severe liver disease (e.g., cirrhosis and HCC). Several microRNAs (e.g., miR-122, miR135a) are supposed to be key mediators of HCV infection progression and development of HCC in infected individuals and associated hepatic comorbidities. In chapter 1, we have illustrated the potential roles of virus-specific proteins in HCV molecular pathogenesis. Herein, we will elucidate the host-specific culprits that subvert, impede or disrupt host cells' communications, cell signaling, and metabolic pathways to propagate HCV infection. We will also elaborate that how the subversion of infected host-cell signaling and metabolic pathways disrupt cellular networks to evolve advanced fibrosis and hepatocarcinogenesis in HCV-infected individuals.<br>