The goal of this proposal is to study the factors influencing the transmission of hepatitis C (HCV) from HIV- and HCV-infected mothers to their offspring, describing the natural history of this process, including the virologic, immunologic, and the genetic factors at play in both preventing transmission and modifying any infection which is not prevented. The following aims are planned:
AIM 1) To describe the natural history of infection by identifying HCV-infected pregnant women and studying their offspring for evidence of HCV infection. This will include the quantitation of HCV during pregnancy in cell-free and cell-associated blood compartments, quantitation of CD4 and HIV viral load, and their correlation with whether HCV transmission occurs. The offspring will be studied prospectively from birth for evidence of HCV infection using PCR and serologic methodologies. The transmission rate in children born to HIV-uninfected mothers will be compared to that in HIV-infected and -uninfected children born to HIV-infected mothers. The effect of HCV infection on liver function will be measured.
AIM 2) To assess the distribution of quasispecies using the heteroduplex mobility assay on plasma and peripheral blood mononuclear cells from HCV-infected mothers during pregnancy, peripartum, and in their respective HCV-infected children. This will determine whether the child is infected with a selected few or unselected viruses present in the mother.
AIM 3) To measure humoral and cell-mediated responses to HCV in both HCV infected and uninfected children born to infected mothers prospectively from birth. The presence or absence of such responses will be correlated with infection status and disease status. The presence or absence of these responses will be correlated with viral diversification that occurs in the child as described in AIM 2.
AIM 4) To determine the HLA status of the HCV-infected mothers and their offspring. The prevalence of alleles in the mother and child will be correlated with whether transmission of HCV occurs. The influence of both maternal and child alleles on transmission will be assessed. The correlation of immune responses measured in AIM 3 and the clinical outcome of HCV infection with HLA alleles in the child will be studied.
| Lechner, F; Sullivan, J; Spiegel, H et al. (2000) Why do cytotoxic T lymphocytes fail to eliminate hepatitis C virus? Lessons from studies using major histocompatibility complex class I peptide tetramers. Philos Trans R Soc Lond B Biol Sci 355:1085-92 |
