Abstract
BackgroundHLA-G gene is a non-classical MHC class 1 molecule that is highly expressed in the trophoblast at the maternal-fetal interface. In an attempt to elucidate possible immunological mechanisms facilitating protection of infants born to human immunodeficiency virus type (HIV-1) infected mothers, we have been studying genetic variations in the coding and untranslated regions of HLA-G antigen between HIV-1-infected mothers and their infected or uninfected infants. This study investigated whether HLA-G DNA sequence variants are associated with perinatal HIV-1 transmission.ResultsGenomic DNA samples were obtained from a nested case-control study of 34 mother-child pairs co-enrolled in a cohort of the Perinatal AIDS Collaborative Transmission Study in New York. The samples were from two groups predominantly of African-American and Hispanic origin: In the first group, both mother and child were HIV-1-infected; in the second group, only the mother was infected while the child remained uninfected. Genotyping of HLA-G gene were performed on the extracted DNA from peripheral blood mononuclear cells using PCR based sequencing and restriction fragment-length polymorphism analyses.Among the studied HLA-G exons, dissimilarities in HLA-G DNA sequence variants between the HIV-1 non-transmitting mother child pairs were mostly observed in exon 8-3'-untranslated region at nucleotide positions T3742A, C3743T, G3777C (P = 0.001). Non-transmitting HIV-1 mother child pairs exhibited dissimilarities at nucleotide position C3743T allele with decreased risk of perinatal HIV-1 transmission, compared with HIV-1 transmitting mother-child pairs carrying this allele (odds ratio 0.02 [95% confidence interval 0.00–0.15] P = 0.00001). In addition, heterozygous dissimilarities at nucleotide positions C634G and 714 insT/G in the 5'-upstream regulatory region were observed between the mother child pairs of the HIV-1-non-transmitting group while homozygous similarities of C634C, and either 714insG/G or mother-child pairs with similar 714insT/G were observed among the transmitting group in the same region.ConclusionThis study identified new variants in the HLA-G gene and provides further evidence that dissimilarities in the HLA-G DNA sequence variants could influence the transmission of HIV-1 from infected mothers to their infants.
Highlights
Human leukocyte antigen G (HLA-G) gene is a non-classical MHC class 1 molecule that is highly expressed in the trophoblast at the maternal-fetal interface
This study identified new variants in the HLA-G gene and provides further evidence that dissimilarities in the HLA-G DNA sequence variants could influence the transmission of HIV1 from infected mothers to their infants
This study suggests the association of the HLA-G sequence variants with increased or decreased risk of perinatal HIV1 transmission
Summary
HLA-G gene is a non-classical MHC class 1 molecule that is highly expressed in the trophoblast at the maternal-fetal interface. MTCT has decreased to approximately 1 or 2% after implementation of universal prenatal HIV counseling and testing, antiretroviral prophylaxis, elective cesarean delivery and avoidance of breastfeeding [3]. Antiretroviral therapy for infected pregnant women has significantly reduced the risk of MTCT in developing countries. It remains important to continue to pursue strategies to make effective antiretroviral interventions available in developing countries, an efficacious vaccine would surely be highly valuable for reduction of MTCT and certainly would be the best strategy for reducing infection spread worldwide among adults. The development of an effective vaccine would be greatly assisted by better understanding of the molecular genetic mechanisms of transmission, including for example, if the host gene immune responses involving the chemokines [4,5], and HLA polymorphisms are involved in host-HIV-1 interactions
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