Genetic Characterization of HIV Type 1gagp17 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.

Evaluation of Genetic Diversity of Human Immunodeficiency Virus Type 1 <i>nef</i> Gene Associated with Vertical Transmission

“…Our findings of a low degree of variability of mother-infant nef sequences are consistent with a previously published analysis of nef sequences from HIV-1-infected individuals [22] and other nef sequences described in HIV databases [43]. In addition, the nef sequences from mother-infant pairs were comparable to other conserved HIV-1 genes, including gag [20,21], vif [69] and vpr [68], from the same mother-infant pairs. We could not demonstrate a correlation between genetic variability and the age of the infected infants, as shown for the envelope V3 region sequences of the same mother-infant pairs [3].…”

Conservation of functional domains and limited heterogeneity of HIV-1 reverse transcriptase gene following vertical transmission

“…Several motifs in reverse transcriptase responsible for primer and template binding and positioning and motifs involved in nucleotide recruitment were conserved in all mother-infant pairs' sequences. The data we show here are comparable to those of our previously analyzed conserved genes, including gag P17MA, vif , vpr , tat and nef [58-62]. Our findings suggest that an intact and functional reverse transcriptase open reading frame is essential for HIV-1 replication in mothers and their infants and low degree of viral heterogeneity is maintained following vertical transmission.…”

Role of placenta in the vertical transmission of human immunodeficiency virus

“…32 Specific amino acids motifs in p17 may be associated with perinatal transmission. 32 Gag p17 heterogeneity is higher in transmitting mothers 33 than gag p17 heterogeneity in nontransmitting mothers. 32 The HIV-1 nucleocapsid, P7 and p6 open reading frames and functional domains are conserved following HIV-1 vertical transmission.…”