NDLI: HLA-A*7401–Mediated Control of HIV Viremia Is Independent of Its Linkage Disequilibrium with HLA-B*5703

Content Provider	PubMed Central
Author	Matthews, Philippa C. Emily, Adland Jennifer, Listgarten Leslie, Alasdair Mkhwanazi, Nompumelelo Carlson, Jonathan M. Harndahl, Mikkel Stryhn, Anette Payne, Rebecca P. Ogwu, Anthony Huang, Kuan-hsiang Gary Frater, John Paolo, Paioni Kloverpris, Henrik Jooste, Pieter Dominique, Goedhals Vuuren, Cloete Van Steyn, Dewald Riddell, Lynn Chen, Fabian Luzzi, Graz Balachandran, Thambiah Ndungâ u, Thumbi Buus, SÃ¸ren Carrington, Mary Shapiro, Roger Heckerman, David Goulder, Philip J. R.
Copyright 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-A7401 is associated with favorable viremic control in extended southern African cohorts of >2100 C-clade–infected subjects. We present evidence that HLA-A7401 operates an effect that is independent of HLA-B5703, 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-A7401 combined with HLA-B57. In common with HLA-B alleles that are associated with effective control of viremia, HLA-A7401 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-A7401–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-A7401–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.
Related Links	http://dx.doi.org/10.4049/jimmunol.1003711
Ending Page	5686
Page Count	12
Starting Page	5675
File Format	PDF
ISSN	15506606
e-ISSN	15506606
Journal	Journal of immunology (Baltimore, Md. : 1950)
Issue Number	10
Volume Number	186
Language	English
Publisher Date	2011-05-15
Access Restriction	Open
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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