Mechanism of cell infection with hepatitis C virus (HCV)--a new paradigm in virus-cell interaction.
Hepatitis C virus (HCV) is an enveloped, single-stranded RNA virus, belonging to the Flaviviridae family. HCV infection is a major cause of chronic hepatitis worldwide, leading to steatosis, liver cirrosis and hepatocellular carcinoma. Significant advances in understanding the mechanisms of HCV infection have been made since the development of a cell culture system reproducing the complete HCV cell cycle in vitro. HCV represents a new paradigm in interactions between the virus and its target cell, the human hepatocyte, due to the central role of lipoproteins in the HCV life cycle. Very low density lipoproteins are required for virus particle assembly and secretion. Upon the release, the infectious virus circulates in the blood as triglyceride-rich particles and infects cells using lipoprotein-receptor dependent mechanisms. HCV cell entry is a multi-step process: heparan sulphate and/or low-density lipoprotein receptor are cell surface factors mediating an initial virus attachment; subsequent virus interaction with tetraspanin CD81 and the human scavenger receptor SR-BI, the main HCV receptors, triggers virus movement to the tight junctions and its uptake via Claudin-1 and occludin. Another originality of HCV is that initiation of productive infection requires dynamic microtubules. Whereas other viruses use kinesin or dynein-dependent transport, HCV exploits mechanisms driven by microtubule polymerization to efficiently infect its target cell, in which virus nucleocapsid protein might play a particular role. An improved of understanding of the cellular events involved in HCV cell entry and transport, leading to the initiation of productive HCV infection, may reveal novel targets for anti-viral interventions.
Budkowska
Agata
A
Institut Pasteur, Hépacivirus et Immunité Innée, 25/28 Rue du Dr. Roux, 75724 Paris Cedex 15, France. agata.budkowska@pasteur.fr
D000998:Antiviral Agents / Q000494:pharmacology; D016174:Hepacivirus / Q000187:drug effects / Q000502:physiology*; D006526:Hepatitis C / Q000188:drug therapy / Q000821:virology; D006801:Humans; D011956:Receptors, Cell Surface
D000998:Antiviral Agents; D011956:Receptors, Cell Surface