EVOLUTION OF HYPERVARIABLE REGION-1 OF HEPATITIS-C VIRUS IN PRIMARY INFECTION

The hypervariable region 1 (HVR-1) of the putative envelope encoding E 2 region of hepatitis C virus (HCV) RNA was analyzed in sequential sam ples from three patients with acute type C hepatitis infected from dif ferent sources to address (i) the dynamics of intrahost HCV variabilit y during the primary infection and (ii) the role of host selective pre ssure in driving viral genetic evolution. HVR-1 sequences from 20 clon es per each point in time were analyzed after amplification, cloning, and purification of plasmid DNA from single colonies of transformed ce lls. The intrasample evolutionary analysis (nonsynonymous mutations pe r nonsynonymous site [K-a], synonymous mutations per synonymous site [ K-s], K-a/K-s ratio, and genetic distances [gd]) documented low gd in early samples (ranging from 2.11 to 7.79%) and a further decrease afte r seroconversion (from 0 to 4.80%), suggesting that primary HCV infect ion is an oligoclonal event, and found different levels and dynamics o f host pressure in the three cases. The intersample analysis (pairwise comparisons of intrapatient sequences; rK(a), rK(s), rK(a)/rK(s) rati o, and gd) confirmed the individual features of HCV genetic evolution in the three subjects and pointed to the relative contribution of eith er neutral evolution or selective forces in driving viral variability, documenting that adaptation of HCV for persistence in vivo follows di fferent routes, probably representing the molecular counterpart of the viral fitness for individual environments.