Hepatitis C virus biology.
Hepatitis C virus infection represents a major problem of public health with around 350 millions of chronically infected individuals worldwide. The frequent evolution towards severe liver disease and cancer are the main features of HCV chronic infection. Antiviral therapies, mainly based on the combination of IFN and ribavirin can only assure a long term eradication of the virus in less than half of treated patients. The mechanisms underlying HCV pathogenesis and persistence in the host are still largely unknown and the efforts made by researchers in the understanding the viral biology have been hampered by the absence of a reliable in vitro and in vivo system reproducing HCV infection. The present review will mainly focus on viral pathogenetic mechanisms based on the interaction of HCV proteins (especially core, NS3 and NS5A) with host cellular signaling transduction pathways regulating cell growth and viability and on the strategies developed by the virus to persist in the host and escape to antiviral therapy. Past and recent data obtained in this field with different experimental approaches will be discussed.
Giannini
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C
Liver Cancer and Molecular Virology, Pasteur-INSERM Unit 370, 156, Rue de Vaugirard 75015 Paris, France.
Bréchot
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C
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D024882:Drug Resistance, Viral / Q000276:immunology*; D016174:Hepacivirus / Q000276:immunology / Q000378:metabolism* / Q000472:pathogenicity; D006526:Hepatitis C / Q000188:drug therapy / Q000276:immunology / Q000821:virology*; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D017361:Viral Nonstructural Proteins / Q000276:immunology*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; D012324:RNA-Dependent RNA Polymerase
D000998:Antiviral Agents; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase