Hepatitis C virus versus innate and adaptive immune responses: a tale of coevolution and coexistence

The virus and its life cycle HCV is an enveloped, positive-stranded RNA virus and represents the Hepacivirus genus in the Flaviviridae family (15).Six major HCV genotypes and more than 100 subtypes have been identified.In the blood of infected patients, HCV is physically associated with VLDL, LDL, and HDL.Entry into hepatocytes requires the tetraspanin CD81 (16), the scavenger receptor class B type I (17), and the tight junction proteins claudin (18, 19) and occludin (20, 21), which confer species specificity (21).HCV also binds to other molecules, such as glycosaminoglycans, the LDL receptor, and the lectins DC-SIGN and L-SIGN, but these are not essential entry factors and do not confer tissue specificity.After clathrin-mediated endocytosis and pH-dependent release from early endosomes, HCV translation and replication start in the cytosol.Translation is initiated through an internal ribosomal entry site in the 5′ untranslated region (UTR) and generates a single polyprotein of approximately 3,000 amino acids that is cleaved by cellular and viral proteases into 10 structural and nonstructural proteins.An alternate open reading frame encodes a short protein of unknown function (Figure 1).Following synthesis and maturation, nonstructural proteins and viral RNA form membraneassociated replication complexes and catalyze the transcription of negative-strand RNA intermediates from which, in turn, progeny positive-strand RNA molecules are generated (15).Capsid proteins and genomic RNA assemble to form a nucleocapsid, which buds through intracellular membranes into cytoplasmic vesicles.Enveloped, mature virions leave the cell via the secretory pathway. Hepatitis C virus versus innate and adaptive immune responses: a tale of coevolution and coexistenceBarbara