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 anti-retroviral 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.
Yedavalli
V R
VR
Department of Microbiology and Immunology, College of Medicine, University of Arizona Health Sciences Center, Tucson, Arizona 85724, USA.
Ahmad
N
N
D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D017124:Conserved Sequence / Q000235:genetics*; D005260:Female; D016346:Gene Products, vif / Q000235:genetics*; D016336:Gene Products, vpr / Q000235:genetics*; D015658:HIV Infections / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D017434:Protein Structure, Tertiary / Q000502:physiology*; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D013223:Statistics as Topic; D054320:vif Gene Products, Human Immunodeficiency Virus; D054325:vpr Gene Products, Human Immunodeficiency Virus
D016346:Gene Products, vif; D016336:Gene Products, vpr; D054320:vif Gene Products, Human Immunodeficiency Virus; D054325:vpr Gene Products, Human Immunodeficiency Virus