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HLA-A*7401-mediated control of HIV viremia is independent of its linkage disequilibrium with HLA-B*5703
- Source :
- Matthews , P C , Adland , E , Listgarten , J , Leslie , A , Mkhwanazi , N , Carlson , J M , Harndahl , M , Buus , A S , Payne , R P , Ogwu , A , Huang , K-H G , Frater , J , Paioni , P , Kloverpris , H , Jooste , P , Goedhals , D , van Vuuren , C , Steyn , D , Riddell , L , Chen , F , Luzzi , G , Balachandran , T , Ndung'u , T , Buus , S , Carrington , M , Shapiro , R , Heckerman , D & Goulder , P J R 2011 , ' HLA-A*7401-mediated control of HIV viremia is independent of its linkage disequilibrium with HLA-B*5703 ' , Journal of Immunology , vol. 186 , no. 10 , pp. 5675-86 .
- Publication Year :
- 2011
-
Abstract
- The potential contribution of HLA-A alleles to viremic control in chronic HIV type 1 (HIV-1) infection has been relatively understudied compared with HLA-B. In these studies, we show that HLA-A*7401 is associated with favorable viremic control in extended southern African cohorts of >2100 C-clade-infected subjects. We present evidence that HLA-A*7401 operates an effect that is independent of HLA-B*5703, with which it is in linkage disequilibrium in some populations, to mediate lowered viremia. We describe a novel statistical approach to detecting additive effects between class I alleles in control of HIV-1 disease, highlighting improved viremic control in subjects with HLA-A*7401 combined with HLA-B*57. In common with HLA-B alleles that are associated with effective control of viremia, HLA-A*7401 presents highly targeted epitopes in several proteins, including Gag, Pol, Rev, and Nef, of which the Gag epitopes appear immunodominant. We identify eight novel putative HLA-A*7401-restricted epitopes, of which three have been defined to the optimal epitope. In common with HLA-B alleles linked with slow progression, viremic control through an HLA-A*7401-restricted response appears to be associated with the selection of escape mutants within Gag epitopes that reduce viral replicative capacity. These studies highlight the potentially important contribution of an HLA-A allele to immune control of HIV infection, which may have been concealed by a stronger effect mediated by an HLA-B allele with which it is in linkage disequilibrium. In addition, these studies identify a factor contributing to different HIV disease outcomes in individuals expressing HLA-B*5703.
Details
- Database :
- OAIster
- Journal :
- Matthews , P C , Adland , E , Listgarten , J , Leslie , A , Mkhwanazi , N , Carlson , J M , Harndahl , M , Buus , A S , Payne , R P , Ogwu , A , Huang , K-H G , Frater , J , Paioni , P , Kloverpris , H , Jooste , P , Goedhals , D , van Vuuren , C , Steyn , D , Riddell , L , Chen , F , Luzzi , G , Balachandran , T , Ndung'u , T , Buus , S , Carrington , M , Shapiro , R , Heckerman , D & Goulder , P J R 2011 , ' HLA-A*7401-mediated control of HIV viremia is independent of its linkage disequilibrium with HLA-B*5703 ' , Journal of Immunology , vol. 186 , no. 10 , pp. 5675-86 .
- Notes :
- English
- Publication Type :
- Electronic Resource
- Accession number :
- edsoai.ocn826494887
- Document Type :
- Electronic Resource