An overview of HCV molecular biology, replication and immune responses

Abstract

Hepatitis C virus (HCV) causes acute and chronic hepatitis which can eventually lead to permanent liver damage, hepatocellular carcinoma and death. Currently, there is no vaccine available for prevention of HCV infection due to high degree of strain variation. The current treatment of care, Pegylated interferon α in combination with ribavirin is costly, has significant side effects and fails to cure about half of all infections. In this review, we summarize molecular virology, replication and immune responses against HCV and discussed how HCV escape from adaptive and humoral immune responses. This advance knowledge will be helpful for development of vaccine against HCV and discovery of new medicines both from synthetic chemistry and natural sources.

Figure 1

Proteins encoded by the HCV genome. HCV is formed by an enveloped particle harbouring a plus-strand RNA of 9.6 kb. The genome carries a long openreading frame (ORF) encoding a polyprotein precursor of 3010 amino acids. Translation of the HCV ORF is directed via a 340 nucleotide long 5' nontranslated region (NTR) functioning as an internal ribosome entry site; it permits the direct binding of ribosomes in close proximity to the start codon of the ORF. The HCV polyprotein is cleaved co- and post-translationally by cellular and viral proteases into ten different products, with the structural proteins (core (C), E1 and E2) located in the N-terminal third and the nonstructural (NS2-5) replicative proteins in the remainder. Putative functions of the cleavage products are shown [4].

Figure 2

HCV receptors for cell entry.