In Tanzania, newborns are infected by HIV-1 subtypes A, C, D and intersubtype recombinants. These HIV-1 subtypes are responsible for almost all HIV-1 infections in infant and adult populations. At the present time, the viral genetic determinant(s) that contribute to perinatal infection are unknown. Our Tanzania mother-child cohort provides a unique population to study the generation of intersubtype recombinants as molecular tools to map viral determinants associated with perinatal transmission in the context of different HIV-1 subtypes. This analysis will include a large number of recombinant genomes with a variety of recombination patterns from transmitting and non- transmitting mothers as well as a detailed genetic analysis of recombinant viruses that were successfully transmitted to infants. To establish if recombinant viruses are better fitted for perinatal transmission than parental genomes, we will sequence a large number of env and gag clones from maternal blood. By comparing the proportion of recombinant viruses in transmitting and non-transmitting mothers we will establish if recombinant viruses have a selective advantage for perinatal transmission. We will sequence full-length recombinant genomes of infected infants to determine if recombinant viruses transmitted perinatally follow particular patterns of genetic exchange associated with increased rates of perinatal transmission. We will sequence full- length recombinant genomes of infected infants to determine if recombinant viruses transmitted perinatally follow particular patterns of genetic exchange associated with increased rates of perinatal transmission. Our preliminary studies suggest that particular regions of the viral genome, such as certain gp120 V3's are over represented in transmitted recombinants. In vitro studies of envelope and LTR regions from recombinant and non-recombinant viruses will give use relevant information about the phenotypes that are generated by the genetic exchange. We believe these studies will contribute to the identification of viral determinants associated with perinatal transmission and to help establish whether genetic differences between HIV-1 subtypes are associated with biological functions. This study may provide information that will eventually be useful for decreasing rates of perinatal infection.
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