EVOLUTION OF HEPATITIS-C VIRUS QUASI-SPECIES IN MOTHERS AND INFANTS INFECTED THROUGH MOTHER-TO-INFANT TRANSMISSION

Background/Aims: Two mother-infant pairs (Pair H and P) were studied t o determine the evolution of hepatitis C virus (HCV) quasispecies. Met hods: Eight clones of the hypervariable region of HCV cDNA from the in fants' sera sampled at the age of 3 months, 1, 2, and 3 years and the time-corresponding maternal sample were also sequenced. The sequences were analyzed by the nucleotide diversity, substitution rate, and phyl ogenetic studies. Results: HCV quasispecies of the infants were more h omogeneous than those of their mothers, particularly at the age of 3 m onths (nucleotide diversity, pi = 0.18 x 10(-2)/site in infant H, and 0.22 x 10(-2)/site in infant P). The nucleotide substitution rate in i nfants also increased as they aged, from 1.2 x 10(-2) to 4.46 x 10(-2) /site/year in infant H, and from 0.21 x 10(-2) to 4.88 x 10(-2)/site/y ear in infant P respectively. The nucleotide sequence differences betw een infants and mothers increased from 2.63 x 10(-2) to 9.06 x 10(-2)/ site in Pair H, and from 1.85 x 10(-2) to 5.33 x 10(-2)/site in Pair P within 3 years. Phylogenetic studies suggest the infants' initial qua sispecies mere closely related to their mothers', while they evolved d ifferently. HCV RNA titer was stable during follow-up and the infants' titer was similar to their mothers'. The fluctuations in titer did no t correlate with nucleotide diversity. Conclusions: HCV quasispecies e volved differently in each individual, even though they were genetical ly linked. The sequence in infants was not as complex as in their moth ers.