Analysis of human immunodeficiency virus type 1 env and gag sequence variants derived from a mother and two vertically infected children provides evidence for the transmission of multiple sequence variants.

Abstract

In order to investigate the transmission of human immunodeficiency virus type 1 (HIV-1) from mother-to-child we have examined serial plasma RNA samples obtained from a mother over an eight year period spanning four pregnancies. Child 1 and 2 (born January 1987 and June 1990) were uninfected whilst child 3 and 4 (born July 1992 and February 1994) were HIV positive. Genetic variation was examined within the viral population of the mother and her two infected children for both the V3 loop and flanking regions of the env gene and the p17 region of the gag gene. In one child (child 4) a highly homogeneous virus population was observed within both env and gag in contrast to the more heterogeneous virus population observed within the mother. Viral sequences of child 4 clustered within a single branch within the reconstructed phylogenetic tree. This is consistent with the transmission of a single maternal variant to the child in this case, which may indicate a selective process. By contrast, child 3 showed substantial genetic heterogeneity even within the first samples obtained shortly after birth. Sequences of child 3 clustered in two distinct groups within the phylogenetic tree and were separated by sequences of the mother. These results are not consistent with the selective transmission of a single maternal variant to the child in this case and we therefore propose that the infection within child 3 is the result of the transmission of multiple sequence variants to the child. All transmitted sequence variants were predicted to be of the macrophage-tropic, nonsyncytium-inducing (NSI) phenotype.