Abstract

Hepatitis C virus (HCV), a virus present in human population from indefinite time period, has affected millions of people globally, by causing liver infection which in majority of cases leads to chronicity, cirrhosis, end stage liver disease and hepatocellular carcinoma (HCC).  The disease burden is expected to increase in the developing and under developed world in future. The distribution of HCV genotypes is changing, as are the modes of transmission. Evolution of HCV is a highly dynamic process as it exploits all known mechanisms of genetic variation including recombination and mutation, to ensure its survival. It occurs both through multiple processes of adaptive selection that drive sequence change and through drift, in which phenotypically neutral sequence changes accumulate over time without altering the phenotype or behaviour of the virus. However, despite its potential to change rapidly, the longer-term evolution of HCV appears to be remarkably conservative. Phylogenetic and statistical models of viral evolution are useful in reconstructing mutational pathways of drug resistance. The two major divisions of viral heterogeneity include genotypes and quasispecies. The rate of nucleotide changes varies significantly among the different regions of the viral genome. The present HCV classification is incomplete, as new genotypes and variants are being identified till yet. Diversification of HCV occurred over time but with different rates. Host immune pressure is thought to be a main factor driving diversification in HCV quasispecies. Core and hypervariable regions are more diverse while 5' un-translated region (UTR) and 3' UTR are highly conserved across the genotypes.

Key words: HCV, phylogeny, 5' UTR, viral evolution, recombination, quasispecies.

Abbreviation

HCV, Hepatitis C virus; HCC, hepatocellular carcinoma; UTR, 5' un-translated region; IRES, internal ribosome entry site; HVR, hypervariable region;PCR, polymerase chain reaction; ELISA, enzyme-linked immunosorbent assay;ORF, open reading frame; dS, synonymous nucleotide substitutions per synonymous site; dN, nonsynonymous nucleotide substitutions per nonsynonymous site; 5'NCR, 5' non-coding region; MSM, male sex with male;CTL, cytotoxic T-lymphocyte.