HCV ReplicaseInteractome a Comprehensive Landscape of Host Factors Orchestrating Viral Replication

Research Article

HCV Replicase Interactome a Comprehensive Landscape of Host Factors Orchestrating Viral Replication

Eleanor Vance^1* , Alistair Chen¹ , Maria Rossi² ,Ingrid Schmidt² , Lars Johansen²

¹Department of Viral Pathogenesis, University of Toronto, Toronto, Ontario, Canada
²Institute of Virology, University of Cambridge, Cambridge, United Kingdom

Available online: 5 July 2010

Abstract

Hepatitis C virus (HCV), a significant global health burden, commandeers a plethora of host cellular proteins to facilitate its intricate replication cycle. The viral RNA-dependent RNA polymerase, NS5B, forms the catalytic core of the multi-protein replicase complex, a dynamic assembly anchored to modified endoplasmic reticulum membranes. Deciphering the complex web of host-virus Protein Protein Interactions (PPIs) within the HCV replicase interactome is pivotal for understanding the fundamental mechanisms of viral propagation and identifying potential Achilles’ heels for therapeutic intervention. This comprehensive review synthesizes the current knowledge of the HCV replicase interactome, encompassing the direct and indirect associations of the viral non-structural proteins (NS3, NS4A, NS4B, NS5A, and NS5B) with host cellular machinery. We meticulously examine the functional roles of these interactions across various stages of the viral lifecycle, including RNA binding, replication complex assembly, membrane remodeling, translation, and immune evasion. Furthermore, we critically evaluate the methodologies employed to map this intricate interactome and underscore the profound implications of these findings for the rational design of novel antiviral strategies. By providing a consolidated and in-depth analysis of the HCV replicaseinteractome, this review aims to foster a deeper understanding of HCV pathogenesis and pave the way for the development of innovative and targeted therapeutic interventions

Keywords

Hepatitis C virus (HCV); Replicase; Antiviral Targets; Protein-Protein Interactions