Evolution of hepatitis C virus quasispecies in mothers and infants infected through mother-to-infant transmission

Abstract

Background/Aims: Two mother-infant pairs (Pair H and P) were studied to determine the evolution of hepatitis C virus (HCV) quasispecies. Methods: Eight clones of the hypervariable region of HCV cDNA from the infants' 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 phylogenetic studies. Results: HCV quasispecies of the infants were more homogeneous than those of their mothers, particularly at the age of 3 months (nucleotide diversity, π= 0.18×10 −2/site in infant H, and 0.22×10 −2/site in infant P). The nucleotide substitution rate in infants also increased as they aged, from 1.2×10 −2 to 4.46×10 −2/site/year in infant H, and from 0.21×10 −2 to 4.88×10 −2/site/year in infant P respectively. The nucleotide sequence differences between infants and mothers increased from 2.63×10 −2 to 9.06×10 −2/site in Pair H, and from 1.85×10 −2/site to 5.33×10 −2/site in Pair P within 3 years. Phylogenetic studies suggest the infants' initial quasispecies were closely related to their mothers', while they evolved differently. HCV RNA titer was stable during follow-up and the infants' titer was similar to their mothers'. The fluctuations in titer did not correlate with nucleotide diversity. Conclusions: HCV quasispecies evolved differently in each individual, even though they were genetically linked. The sequence in infants was not as complex as in their mothers.