112 MODULATING RISK OF HETEROSEXUAL HIV-1 INFECTION BY NON-CLASSICAL MHC CLASS I HLA-E AND HLA-G MOLECULES J Lajoie, M Roger Objective: Heterosexual transmission of HV-1 is the major route of infection worldwide. The non-classical MHC class I HLA-E and HLA-G molecules act as powerful modulators of the innate immune response. HLA-G and HLA-E molecules are involved in the inhibition or activation of NK-mediated cytotoxic responses and could permit or even promote the propagation of infection in the female reproductive tract. We examined whether HLA-E and/or HLA-G genetic variants are associated with the risk of heterosexual HIV-1 infection.
Centre de recherche du CHUM, Université de Montréal, Montréal, Québec
Methods: A total of 397 (228 HIV-1 positive and 169 HIV-1 negative) Zimbabwean women were studied. HLA-E and -G polymorphisms were determined on DNA samples by amplified-restriction fragment length polymorphism (A-RFLP) and DNA sequencing analyses.
Results: The HLA-EG genetic variant alone is significantly associated with a 4.0-fold reduced risk of HIV-1 infection in Zimbabwean women (Odds ratio [OR], 0.29; 95% confidence interval [CI], 0.16-0.51; P=0.001). HLA-G*0105N, which does not encode functional HLA-G1 proteins, was significantly associated with a 2.0-fold reduced risk of HIV-1 infection (OR, 0.45; 95% CI, 0.26-0.79; P=0.005). Furthermore, women carrying the combined protective HLA-EG homozygote/ HLA-G*0105N heterozygote genotype had a 12.8-fold reduced risk of HIV-1 infection compared with those harboring neither genotype (OR: 0.078; 95% CI, 0.008-0.73; P=0.03). These associations remained significant after adjusting for other significant socio-demographic risk factors for HIV prevalence in this population.
Conclusion: In conclusion, HLA-E and HLA-G polymorphisms can independently and synergistically influence susceptibility to heterosexual acquisition of HIV-1 infection. Targeted interventions to modulate HLA-E and -G expression in genital tissues could lead to novel strategies for the prevention of heterosexual HIV-1 transmission.
The complete study was published in JID 2006:193: 298-301
This study was supported by Fonds de la recherche en santé du Québec