Hepatitis C virus is a major world health problem. HCV infections progress from chronic liver disease to cirrhosis, hepatocarcinoma and liver failure. Two key aspects of the HCV lifecycle are entry and assembly. Here, we explore entry where new factors and pathways continue to be discovered.
The HCV lifecycle begins with the virus and serum lipoproteins forming hybrid ‘lipoviral particles’. LVP’s protect from antibody neutralization and facilitate entry. Once an LVP leaves the bloodstream and reaches a hepatocyte, surface receptors create low affinity bonds with ApoE.
The LVP then binds with SRB1, activating a cluster of co-receptors and exposing the binding site for CD-81. Signal transduction is initiated, promoting lateral movement of the viral complex to a hepatocyte tight junction.
As the complex reaches a tight junction, CD81 interacts with claudin 1. Claudin 1 is an essential factor for HCV entry, inducing clathrin-mediated endocytosis.
The low endosomal pH causes a conformational change in the viral E proteins resulting in an HCV-endosome fusion. This event permits the virus to escape, uncoat, and release its genome into the cytosol for translation and replication.
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