Associations between MHC class I and susceptibility to HIV-2 disease progression.
OBJECTIVE
Human immunodeficiency virus type 2 (HIV-2) progression to disease is significantly slower than that of human immunodeficiency virus type 1 (HIV-1). Genetic determinants for susceptibility to disease progression were hypothesized to play a more significant role in this infection compared with HIV-1. We sought to identify common human lymphocyte antigen (HLA) alleles in the Senegalese population and to compare HLA profiles between HIV-2-infected individuals with low and high risk for disease progression.


METHODS
We conducted a case-control study investigating possible associations between MHC class I genes and the risk of disease progression in HIV-2-infected individuals. The MHC class I genotype was molecularly defined using polymerase chain reaction with sequence specific primers (PCR-SSP) in 62 female sex workers from the Dakar, Senegal cohort. Lack of antibodies to the HIV-2 antigen p26 has been previously shown to predict disease progression and was used in this study as a surrogate marker. Twenty-one cases were identified lacking antibodies to p26, therefore at a higher risk of disease progression, and were compared with 41 p26 antibody-positive, randomly selected controls.


RESULTS
Statistical analysis showed that HLA B35 was significantly associated with lack of p26 antibodies, and higher risk of disease progression ( < 0.05). The same association was found for the self-defined class I haplotypes B35-Cw4 and A23-Cw 7 ( < 0.05). The HLA B 53 allele was associated with slower disease progression; however, this association was not statistically significant. We observed a trend whereby heterozygotes were at lower risk for HIV-2 disease progression, as previously reported in HIV-1 disease.


CONCLUSIONS
In this West African population, a distinct profile of HLA class I alleles was observed, and many of these appear to influence disease progression in HIV-2 infection.
D000483:Alleles; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D015683:Gene Products, gag / Q000276:immunology; D005805:Genes, MHC Class I; D020022:Genetic Predisposition to Disease; D015483:HIV Antibodies / Q000097:blood; D015488:HIV Antigens / Q000276:immunology; D015658:HIV Infections / Q000235:genetics / Q000503:physiopathology* / Q000821:virology; D015498:HIV-2 / Q000276:immunology; D015797:HLA-B35 Antigen / Q000235:genetics; D006801:Humans; D012675:Senegal; D011477:Sex Work; D054301:gag Gene Products, Human Immunodeficiency Virus
D015683:Gene Products, gag; D015483:HIV Antibodies; D015488:HIV Antigens; D015797:HLA-B35 Antigen; D054301:gag Gene Products, Human Immunodeficiency Virus; C065558:gag protein p26, Human immunodeficiency virus