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Background: There is little data on the evolution of hepatitis C virus (HCV) quasispecies in infants infected by mother-to-infant transmission during long-term follow up. The hypervariable region 1 (HVR1) of the HCV genome was investigated in two mother–infant pairs from birth to 7.6 and 10.2 years, respectively.Methods: Ten cDNA clones of HVR1 generated from HCV-RNA and extracted from serum samples of both pairs were analyzed. The sequences were compared with regard to variability, identity, and hydrophobia profile, and analyzed by phylogenetic studies.Results: The alanine aminotransferase (ALT) level was high with fluctuation in infant A and almost within the normal range in infant B. Sequence diversity was higher in infant A at 7.6 years than in infant B at 9.3 years (sequence identity with the mothers’; 69.3–70.7% vs 85.3–90.7% for nucleotides, and 48% vs 68–72% for amino acids, respectively). Compared to the first samples, amino acid changes greatly increased in infant A (35.2% at 4.9 years and 52% at 7.6 years), but not in infant B (4% at 5.6 years and 27.5% at 9.3 years). Phylogenetic studies revealed that quasispecies in infant A evolved to a greater extent than that in infant B. Hydrophobia profile analyses revealed that dynamic shifts between hydrophilia and hydrophobia occurred in both infants.Conclusions: As in adults, the evolution of HVR1 and variability of quasispecies increased in infants infected through mother-to-infant transmission for 10 years after birth. A large episode of ALT elevation suggested the emergence of escape mutants and the evolution of new quasispecies. [ABSTRACT FROM AUTHOR]

Abstract Background: Hepatitis C virus (HCV) particles in sera can be divided into two classes: low-density free particles and high-density immune complex particles. Previous studies have revealed that the clinical progression of HCV infection is closely associated with the occurrence of the former class, rather than the latter, in an experimental chimpanzee model and in HCV-infected adult cases. Methods: To verify this concept in infantile cases, we prospectively analysed HCV particle populations, fractionated according to buoyant density, in serum samples from five infants infected by mother-to-infant transmission. Results: In all five cases, HCV particles were predominantly high density at the age of one month. In four of five cases, low-density HCV particles became predominant in association with a decrease in maternally transmitted antibody levels. In one case, in which high serum levels of alanine aminotransferase persisted, low-density particles were predominant between the ages of 3 and 9 months, in three consecutive samples. In other cases, in which infants were asymptomatic or had transient hepatitis, low-density HCV particles were predominant at only one sampling point or not at all throughout the follow-up period. Conclusions: Maternal antibody transmitted via the placenta reacts with the HCV particles in infants infected through vertical transmission. A decrease in maternal antibody levels results in an increase in low-density free virions. It is suggested that low-density particles play an important role in liver inflammation. [ABSTRACT FROM AUTHOR]