Review Article: Novel Therapeutic Options for Chronic Hepatitis C

Evangelos Cholongitas; George V. Papatheodoridis

Disclosures

Aliment Pharmacol Ther. 2008;27(10):866-884. 

In This Article

HCV Virion and Its Life Cycle

Hepatitis C virus is a small enveloped virus with a 9.6 kb positive-sense single-stranded RNA genome that encodes a unique large polyprotein, which is processed by cellular and virally encoded proteases to produce at least 10 mature structural and nonstructural (NS) proteins (Figure 2).[8] Amongst the structural proteins, the two envelope glycoproteins, E1 and E2, are essential components of the HCV virion envelope and are necessary for viral entry and fusion with cellular membrane.[9] The latter is an important step for the release of HCV nucleocapsid in the cell cytoplasm and initiation of HCV polyprotein translation in a membranous web made of the NS proteins and host cell proteins called 'replication complex', located in close contact with perinuclear membranes.[8] HCV 5'-nontranslated region contains a highly structured element, called internal ribosome entry site (IRES), which is essential for the initiation of HCV polyprotein translation.[10] Amongst the NS proteins, the NS3 serine-like protease and the RNA-dependent RNA polymerase (RdRp), which is encoded by the NS5 region, are essential for viral maturation and replication, and therefore represent ideal targets for the development of small molecule anti-HCV compounds.[11,12] Genome encapsidation occurs in the endoplasmic reticulum and nucleocapsids are enveloped and matured into the Golgi apparatus before they are released in the pericellular space by exocytosis (Figure 1).[13]

Structure of the 9.6 kb positive-sense single-stranded RNA genome of hepatitis C virus that encodes the structural and nonstructural proteins of the virus.

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