Mother-to-child transmission of HIV-1: Strong association with certain maternal HLA-B alleles independent of viral load implicates innate immune mechanisms

Robert Winchester, Jane Pitt, Manhattan Charurat, Laurence S. Magder, Harald H.H. Göring, Alan Landay, Jennifer S. Read, William Shearer, Edward Handelsman, Katherine Luzuriaga, George V. Hillyer, William Blattner

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)659-670
Number of pages12
JournalJournal of Acquired Immune Deficiency Syndromes
Volume36
Issue number2
DOIs
StatePublished - Jun 1 2004
Externally publishedYes

Keywords

  • HIV-1 vertical transmission
  • HLA-B alleles
  • KIR3DL1 receptor
  • NK receptor
  • Viral load

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

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    Winchester, R., Pitt, J., Charurat, M., Magder, L. S., Göring, H. H. H., Landay, A., Read, J. S., Shearer, W., Handelsman, E., Luzuriaga, K., Hillyer, G. V., & Blattner, W. (2004). Mother-to-child transmission of HIV-1: Strong association with certain maternal HLA-B alleles independent of viral load implicates innate immune mechanisms. Journal of Acquired Immune Deficiency Syndromes, 36(2), 659-670. https://doi.org/10.1097/00126334-200406010-00002