Human Leukocyte Antigen B58 Supertype and Human Immunodeficiency Virus Type 1 Infection in Native Africans

Department of Epidemiology, University of Alabama at Birmingham, AL 35294, USA.
Journal of Virology (Impact Factor: 4.44). 06/2006; 80(12):6056-60. DOI: 10.1128/JVI.02119-05
Source: PubMed


Human leukocyte antigen (HLA) class I alleles can be grouped into supertypes according to their shared peptide binding properties.
We examined alleles of the HLA-B58 supertype (B58s) in treatment-naïve human immunodeficiency virus type 1 (HIV-1)-seropositive
Africans (423 Zambians and 202 Rwandans). HLA-B and HLA-C alleles were resolved to four digits by a combination of molecular
methods, and their respective associations with outcomes of HIV-1 infection were analyzed by statistical procedures appropriate
for continuous or categorical data. The effects of the individual alleles on natural HIV-1 infection were heterogeneous. In
HIV-1 subtype C-infected Zambians, the mean viral load (VL) was lower among B*5703 (P = 0.01) or B*5703-Cw*18 (P < 0.001) haplotype carriers and higher among B*5802 (P = 0.02) or B*5802-Cw*0602 (P = 0.03) carriers. The B*5801-Cw*03 haplotype showed an association with low VL (P = 0.05), whereas B*5801 as a whole did not. Rwandans with HIV-1 subtype A infection showed associations of B*5703 and B*5802
with slow (P = 0.06) and rapid (P = 0.003) disease progression, respectively. In neither population were B*1516-B*1517 alleles associated with more favorable
responses. Overall, B58s alleles, individually or as part of an HLA-B-HLA-C haplotype, appeared to have a distinctive impact
on HIV-1 infection among native Africans. As presently defined, B58s alleles cannot be considered uniformly protective against
HIV/AIDS in every population.

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    • "However, only a third of HLA matched hosts mount an epitope-specific response [41]; and the six major MHC determinants of HIV-1 protection in Caucasians [42] lacked protective associations in African cohorts [26]. It is also unclear why the widely protective HLA B*5801 [18] [43] [44] lacked protection in clade A-infected Rwandans [45]. Others also demonstrated higher A163X frequencies among clade A subjects [27]. "
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    • "A follow up study from the same group showed that peptide presentation properties of particular B*35 subtypes explain much of this association [38]. The dominance of HLA-B in the control of HIV-1 infection is supported by several studies which associated HLA-B*57, B*5801 and B*27 with slower disease progression rates (time to AIDS) and strong virologic (viral load) and immunologic control (CD4 count) [39-48], while B*35, B*5802 and B*18 were associated with ineffective control of viral replication and rapid progression to AIDS [37,43,44,47,49,50]. In addition, a significantly greater number of CD8+ T cell responses are HLA-B restricted, compared to HLA-A and -C. "
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    • "Their allelic variants have been associated with various outcomes in the natural course of HIV-1 infection, including viremia and disease progression (time to manifest immunodeficiency after infection) [9], [10], [11], [12], [13], [14], [15]. Favorable HLA alleles like HLA-B*57 and B*27 have strong and durable impact on both early and late outcomes including set-point VL [6], [16], [17], [18], [19], [20], [21], [22], and they appear to reduce or delay viral transmission by suppressing viremia in an infected potential transmitter (e.g., a sexual partner) [6],[21]. In contrast, evidence that HLA variants influence acquisition in HESNs is less convincing; associations reported for various class I alleles (A*23, A*68:02, A*74 and B*18) have been less consistent in studies of mother-infant pairs [23], [24], commercial sex workers [25], [26], [27] and other high-risk groups [28]. "
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