Genetic characterization of HIV type 1 gag p17 matrix genes in isolates from infected mothers lacking perinatal transmission

Abstract

The gag p17 matrix sequences of human immunodeficiency virus type 1 (HIV-1) were analyzed from three nontransmitting mothers (mothers who failed to transmit HIV-1 to their infants in the absence of antiretroviral therapy), including multiple deliveries in the case of mother 3. There was a low degree of heterogeneity of gag p17 matrix sequences in nontransmitting mothers compared with our previously analyzed mother-infant pairs' sequences. Whereas most of the functional domains essential for p17 matrix function were generally conserved, the polymerization site was less conserved. Several amino acid motifs, including KIEEEQN (positions 103-109) at the major antibody-binding site, were variable and the C-terminal 6-mer QVSQNY, a lysine or glutamine at position 15, an alanine at position 54, a lysine at position 76, a valine at position 104, and an aspartic acid at positions 102 and 121 were conserved in nontransmitting mothers' sequences compared with transmitting mothers' sequences. Phylogenetic analyses of 82 p17 matrix sequences revealed distinct clusters for each nontransmitting mother. Some of these motifs in gag p17 matrix sequences that are present in nontransmitting mothers and absent in transmitting mothers could be used as new targets for the development of preventive strategies for perinatal transmission.