ANALYSIS OF ENVELOPE SEQUENCE VARIANTS SUGGESTS MULTIPLE MECHANISMS OF MOTHER-TO-CHILD TRANSMISSION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1

In order to elucidate the molecular mechanisms involved in human immunodeficiency virus type 1 (HIV-1) mother-to child transmission, we have analyzed the genetic variation within the V3 hypervariable domain and flanking regions of the HIV-1 envelope gene in four mother-child transmission pairs, Phylogenetic analysis and amino acid sequence comparison were performed on cell-associated viral sequences derived from maternal samples collected at different time points during pregnancy, after delivery, and from child samples collected from the time of birth until the child was approximately 1 year of age. Heterogeneous sequence populations were observed to be present in all maternal samples collected during pregnancy and postdelivery. In three newborns, viral sequence populations obtained within 2 weeks after birth revealed a high level of V3 sequence variability, In contrast, V3 sequences obtained from the fourth child (diagnosed at the age of 1 month) displayed a more restricted heterogeneity. The phylogenetic analysis performed for each mother-child sequence set suggested that several mechanisms may potentially be involved in HIV-1 vertical transmission, For one pair, child sequences were homogeneous and clustered in a single branch within the phylogenetic tree, consistent with selective transmission of a single maternal variant. For the other three pairs, the child sequences were more heterogeneous and clustered in several separate branches within the tree, In these cases, it appeared likely that more than one maternal variant was responsible for infection of the child, In conclusion, no single mechanism can account for mother-to-child HIV-1 transmission; both the selective transmission of a single maternal variant and multiple transmission events may occur.