ANALYSIS OF GENETIC-HETEROGENEITY, ANTIGENICITY, AND BIOLOGICAL CHARACTERISTICS OF HIV-1 IN A MATERNAL TRANSMITTER AND NONTRANSMITTER PATIENT PAIR

To obtain insight into the factors involved in vertical transmission, we compared the sequence diversity, seroreactivity, and biological cha racteristics of human immunodeficiency virus type 1 (HIV-1) derived fr om a transmitter and nontransmitter mother pair. Forty-two clones from the transmitter and 20 from the nontransmitter, spanning the principa l neutralization determinant (PND) of the env gene, were sequenced and analyzed. The intrapatient sequence variation in transmitter and nont ransmitter viruses was 12% and 36%, respectively, and the interpatient variation was 38%. In an effort to correlate immune responses to vira l genetics, we analyzed the sera from these patients against a number of V3 peptides from known HIV-1 isolates, We observed that (i) both th e transmitter and nontransmitter sera demonstrated higher binding to V 3 peptides based on SF-2 and MN sequences than to IIIB and Z6 isolates ; (ii) the vertical transmission of HIV-1 is correlated with the absen ce of high maternal antibody responses to the PND; and (iii) the high- affinity binding of the sera to SF-2 and MN V3 peptides correlated wit h the sequence analysis, indicating that the V3 sequences from both pa tients are more closely related to ADA, SF-162, and MN than to IIIB or Z6. Biological analysis of the viruses from these patients demonstrat e that the transmitters' viruses infect a number of T-cell lines in vi tro, whereas the nontransmitter viruses do not infect cell lines or th e primary lymphocytes.