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Evolution in the hypervariable region of hepatitis C virus in infants after vertical transmission
J Murakami1, M Okamoto, H Miyata
1Department of Pediatrics, Faculty of Medicine, Tottori University, Yonago, Japan.
Insights
Hepatitis C virus (HCV) transmission from mother to infant involves diverse viral clones, not just a single one. Infant HCV evolution, including quasispecies emergence, precedes antibody response and reflects immune system development.
Area of Science:
- Virology
- Immunology
- Hepatology
Background:
- Hepatitis C virus (HCV) infection poses risks during pregnancy.
- Understanding mother-to-infant HCV transmission is crucial for prevention and treatment strategies.
Purpose of the Study:
- To investigate the clonal evolution of HCV during perinatal transmission.
- To analyze the characteristics of transmitted HCV clones and their relationship to maternal viral populations.
Main Methods:
- Prospective analysis of HCV hypervariable region clones in four mother-infant pairs.
- Comparison of viral clones from maternal and infant samples using RNA analysis.
- Monitoring of HCV RNA titers and alanine aminotransferase levels in infants over time.
Main Results:
- HCV RNA was detected in infants shortly after birth, with high viral loads within two months.
- Transmitted HCV clones in infants were closely related to maternal clones but not limited to single or minor populations.
- HCV clones from the low-density fraction in mothers were not transmitted; their proportion increased in infants later, correlating with immune response.
Conclusions:
- Perinatal HCV transmission involves a diverse set of viral clones.
- The emergence of HCV quasispecies in infants precedes their antibody response, indicating viral evolution during early infection.
- Changes in HCV low-density fraction in infants suggest an evolving immune response.
Abstract:
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.