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.
Keywords: ANGPTL-3, ANGPTL-4, Cytokines, Cell signaling, FAS ligand, Gene polymorphism, Hepatocellular carcinoma, Host factors, Interferon lambda 4, Lipid metabolism, Liver cancer risk, Liver fibrosis, MicroRNA, MiR-122, MiR-135a, Metabolic pathways, Nuclear factor-ƙB, PPP2R5D, Toll-like receptors, Tumor necrosis factor-α.
