Evolution in the hypervariable region of hepatitis C virus in infants after vertical transmission

To elucidate the clonal evolution of hepatitis C virus (HCV) during mother-to-infant transmission, we prospectively analyzed HCV clones of the hypervariable region in four HCV RNA-positive infants and compared them with those of the mother. Cord blood samples from three of the four infants were positive for the HCV RNA (< or =10(3) copies/mL), and all of the four infants had the HCV RNA titer of >10(6) copies/mL within 2 mo after birth. The hypervariable region clones detected in the infants were closely related to those in the respective mothers. The results suggest the perinatal transmission of HCV. The hypervariable region clones transmitted to infants were not a single selected clone or minor clones in the mother. None of the clones specific to the low-density fraction in the mother was transmitted to the infants. Moreover, the proportion of HCV in the low-density fraction was minimal in the first few months of life, but increased several months after birth in association with the elevation of alanine aminotransferase. These results suggest that the increase of HCV in the low-density fraction reflect the evolution of immune response in infants. We also demonstrated that the emergence of quasispecies in infants precedes the infantile antibody response.