Genetic analysis of viral variants selected in transmission of human immunodeficiency viruses to newborns

Our previous studies have indicated that HIV transmission from infected mot hers to infants occurs with viruses showing rapid kinetics of replication, and either resistance to maternal neutralizing antibodies or sensitivity to enhancing antibodies. The genotypic patterns that result in these and othe r phenotypic viral characteristics may provide clues to the selection press ures exerted during this mode of transmission. For this reason, DNA sequenc es of the envelope gene (env) were determined for viral isolates obtained f rom seropositive women who were mothers of either infected or uninfected in fants. Sequences of viruses isolated early in life from the infected newbor ns were also determined, such that diversity both within isolates and betwe en maternal and infant isolates could be assessed. Among isolates obtained from mothers of uninfected infants, the V3 region of env demonstrated a hig her degree of heterogeneity than those from mothers of infected infants. Si milar to the viruses obtained from the mothers of infected infants, the inf ant-derived viral sequences were relatively homogeneous. Finally, the react ivity of maternal plasma with infant-derived HIV isolates, whether via neut ralizing or enhancing antibodies, appeared to predict the distribution of v iral sequences in the infant isolates. These data suggest that selective pr essure on HIV-1 during transmission or growth in the infected infant may be mediated by biologic and/or immunologic processes.