TY - JOUR
T1 - Mother-to-child transmission of HIV-1
T2 - Strong association with certain maternal HLA-B alleles independent of viral load implicates innate immune mechanisms
AU - Winchester, Robert
AU - Pitt, Jane
AU - Charurat, Manhattan
AU - Magder, Laurence S.
AU - Göring, Harald H.H.
AU - Landay, Alan
AU - Read, Jennifer S.
AU - Shearer, William
AU - Handelsman, Edward
AU - Luzuriaga, Katherine
AU - Hillyer, George V.
AU - Blattner, William
PY - 2004/6/1
Y1 - 2004/6/1
N2 - The transmission of HIV-1 from mother to child during pregnancy is unlike other types of HIV-1 transmission because the child shares major histocompatibility complex (MHC) genes with the mother during a time while the mother is induced to tolerate the paternally derived fetal MHC molecules, in part through natural killer (NK) recognition of MHC polymorphisms. The relevance of these immune mechanisms to HIV-1 transmission was assessed by determining the HLA-B alleles of mother and infant. Almost half (48%) of mothers who transmitted with low viral loads had HLA-B*1302, B*3501, B*3503, B*4402, or B*5001 alleles, compared with 8% of nontransmitting mothers (P = 0.001). Conversely, 25% of mothers who did not transmit despite high viral loads had B*4901 and B*5301, vs. 5% of transmitting mothers (P = 0.003), a pattern of allelic involvement distinct from that influencing HIV-1 infection outcome. The infant's HLA-B alleles did not appear associated with transmission risk. The HLA-B*4901 and B*5301 alleles that were protective in the mother both differed respectively from the otherwise identical susceptibility alleles, B*5001 and B*3501, by 5 amino acids encoding the ligand for the KIR3DL1 NK receptor. These results suggest that the probable molecular basis of the observed association involves definition of the maternal NK recognition repertoire by engagement of NK receptors with polymorphic ligands encoded by maternal HLA-B alleles, and that the placenta is the likely site of the effect that appears to protect against transmission of maternal HIV-1 through interrelating adaptive and innate immune recognition.
AB - The transmission of HIV-1 from mother to child during pregnancy is unlike other types of HIV-1 transmission because the child shares major histocompatibility complex (MHC) genes with the mother during a time while the mother is induced to tolerate the paternally derived fetal MHC molecules, in part through natural killer (NK) recognition of MHC polymorphisms. The relevance of these immune mechanisms to HIV-1 transmission was assessed by determining the HLA-B alleles of mother and infant. Almost half (48%) of mothers who transmitted with low viral loads had HLA-B*1302, B*3501, B*3503, B*4402, or B*5001 alleles, compared with 8% of nontransmitting mothers (P = 0.001). Conversely, 25% of mothers who did not transmit despite high viral loads had B*4901 and B*5301, vs. 5% of transmitting mothers (P = 0.003), a pattern of allelic involvement distinct from that influencing HIV-1 infection outcome. The infant's HLA-B alleles did not appear associated with transmission risk. The HLA-B*4901 and B*5301 alleles that were protective in the mother both differed respectively from the otherwise identical susceptibility alleles, B*5001 and B*3501, by 5 amino acids encoding the ligand for the KIR3DL1 NK receptor. These results suggest that the probable molecular basis of the observed association involves definition of the maternal NK recognition repertoire by engagement of NK receptors with polymorphic ligands encoded by maternal HLA-B alleles, and that the placenta is the likely site of the effect that appears to protect against transmission of maternal HIV-1 through interrelating adaptive and innate immune recognition.
KW - HIV-1 vertical transmission
KW - HLA-B alleles
KW - KIR3DL1 receptor
KW - NK receptor
KW - Viral load
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U2 - 10.1097/00126334-200406010-00002
DO - 10.1097/00126334-200406010-00002
M3 - Article
C2 - 15167284
AN - SCOPUS:2542492315
SN - 1525-4135
VL - 36
SP - 659
EP - 670
JO - Journal of Acquired Immune Deficiency Syndromes
JF - Journal of Acquired Immune Deficiency Syndromes
IS - 2
ER -