Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
19
pubmed:dateCreated
2010-9-8
pubmed:abstractText
Previous studies have identified a central role for HLA-B alleles in influencing control of HIV infection. An alternative possibility is that a small number of HLA-B alleles may have a very strong impact on HIV disease outcome, dominating the contribution of other HLA alleles. Here, we find that even following the exclusion of subjects expressing any of the HLA-B class I alleles (B*57, B*58, and B*18) identified to have the strongest influence on control, the dominant impact of HLA-B alleles on virus set point and absolute CD4 count variation remains significant. However, we also find that the influence of HLA on HIV control in this C-clade-infected cohort from South Africa extends beyond HLA-B as HLA-Cw type remains a significant predictor of virus and CD4 count following exclusion of the strongest HLA-B associations. Furthermore, there is evidence of interdependent protective effects of the HLA-Cw*0401-B*8101, HLA-Cw*1203-B*3910, and HLA-A*7401-B*5703 haplotypes that cannot be explained solely by linkage to a protective HLA-B allele. Analysis of individuals expressing both protective and detrimental alleles shows that even the strongest HLA alleles appear to have an additive rather than dominant effect on HIV control at the individual level. Finally, weak but significant frequency-dependent effects in this cohort can be detected only by looking at an individual's combined HLA allele frequencies. Taken together, these data suggest that although individual HLA alleles, particularly HLA-B, can have a strong impact, HIV control overall is likely to be influenced by the additive effect of some or all of the other HLA alleles present.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1098-5514
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
84
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
9879-88
pubmed:dateRevised
2010-10-4
pubmed:meshHeading
pubmed-meshheading:20660184-Adult, pubmed-meshheading:20660184-Alleles, pubmed-meshheading:20660184-CD4 Lymphocyte Count, pubmed-meshheading:20660184-Cohort Studies, pubmed-meshheading:20660184-Gene Frequency, pubmed-meshheading:20660184-Genes, MHC Class I, pubmed-meshheading:20660184-Genotype, pubmed-meshheading:20660184-HIV Infections, pubmed-meshheading:20660184-HIV-1, pubmed-meshheading:20660184-HLA-B Antigens, pubmed-meshheading:20660184-HLA-C Antigens, pubmed-meshheading:20660184-Haplotypes, pubmed-meshheading:20660184-Heterozygote, pubmed-meshheading:20660184-Homozygote, pubmed-meshheading:20660184-Host-Pathogen Interactions, pubmed-meshheading:20660184-Humans, pubmed-meshheading:20660184-South Africa, pubmed-meshheading:20660184-Viral Load, pubmed-meshheading:20660184-Virus Replication
pubmed:year
2010
pubmed:articleTitle
Additive contribution of HLA class I alleles in the immune control of HIV-1 infection.
pubmed:affiliation
Weatherall Institute of Molecular Medicine, University of Oxford, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural