Low conservation of functional domains of HIV type 1 vif and vpr genes in infected mothers correlates with lack of vertical transmission

Human immunodeficiency virus type 1 (HIV-1) vif and vpr sequences were analyzed from four nontransmitting mothers (infected mothers who failed to transmit HIV-1 to their infants mainly in the absence of antiretroviral therapy), including a mother with multiple deliveries, and compared with the vif and vpr sequences of five and six previously analyzed transmitting mothers, respectively. In contrast to a high functional conservation of vif and vpr genes in transmitting mother isolates, we found that there was a low degree of conservation of functional domains of these genes in nontransmitting (NT) mother isolates. For vif sequences, NT-2 contained stop codons and no initiation codons, whereas NT-1 sequences carried a substitution of a highly conserved tyrosine to histidine at position 30. In addition, NT-3 and NT-4 sequences contained additional substitutions, including asparagine at position 22, lysine at position 77 and histidine at position 110, that were absent in transmitting mother and consensus subtype B sequences. Similarly, the vpr sequences of NT-2 contained stop codons and no initiation codons, NT-4 contained a substitution of serine in place of alanine at position 30, some NT-1 sequences substituted arginine in place of glycine at position 75, and NT-3 sequences presented a deletion in the C terminus that was absent in transmitting mother and consensus subtype B sequences and is essential for Vpr function. Furthermore, vif and vpr sequences of nontransmitting mothers were less heterogeneous compared with transmitting mother sequences. In conclusion, a low degree of conservation of functional domains and heterogeneity of HIV-1 vif and vpr genes in these infected mothers correlates with lack of vertical transmission.