Characterization of mother-infant HIV type 1 gag p17 sequences associated with perinatal transmission

Abstract

The gag p17 matrix sequences of human immunodeficiency virus type 1 (HIV-1) from seven infected mother-infant pairs were analyzed after perinatal transmission. The p17 matrix open reading frame was maintained in 143 of the 166 clones analyzed (86.2% frequency of intact p17 open reading frames). The functional domains essential for p17 matrix function in HIV-1 replication, including targeting of Gag to the plasma membrane, virus assembly and release, envelope glycoprotein incorporation into virus particle, virus entry, and localization of the virus preintegration complex to the nucleus of nondividing cells, were highly conserved in most of the sequences. In addition, examination of the three-dimensional structure of the p17 matrix protein in mother-infant isolates showed a high degree of conservation of amino acids required for correct folding and biological activity. Several amino acid motifs common to most of the mother-infant pairs sequences, including pair-specific signature sequences, were observed. There was a low degree of heterogeneity of gag p17 sequences within mothers, within infants, and between mother-infant pairs, but the distances were greater between epidemiologically unlinked individuals. Phylogenetic analyses of 166 mother-infant pairs and 181 other p17 sequences available from HIV-1 databases revealed distinct clusters for each mother-infant pair and for other p17 sequences. In conclusion, these findings indicate that an intact and functional gag p17 matrix is maintained during maternal-fetal transmission and that several motifs in p17 may be associated with perinatal transmission.