| Literature DB >> 35841889 |
Shuying S Li1, Andrew Hickey2, Shida Shangguan3, Philip K Ehrenberg4, Aviva Geretz3, Lauryn Butler3, Gautam Kundu3, Richard Apps5, Matthew Creegan3, Robert J Clifford3, Suteeraporn Pinyakorn3, Leigh Anne Eller3, Pikunchai Luechai2, Peter B Gilbert1, Timothy H Holtz6, Anupong Chitwarakorn7, Carlo Sacdalan8, Eugène Kroon8, Nittaya Phanuphak8, Mark de Souza8, Jintanat Ananworanich9, Robert J O'Connell10, Merlin L Robb3, Nelson L Michael10, Sandhya Vasan3, Rasmi Thomas11.
Abstract
Human leukocyte antigen (HLA) alleles have been linked to HIV disease progression and attributed to differences in cytotoxic T lymphocyte (CTL) epitope representation. These findings are largely based on treatment-naive individuals of European and African ancestry. We assessed HLA associations with HIV-1 outcomes in 1,318 individuals from Thailand and found HLA-B∗46:01 (B∗46) associated with accelerated disease in three independent cohorts. B∗46 had no detectable effect on HIV-specific T cell responses, but this allele is unusual in containing an HLA-C epitope that binds inhibitory receptors on natural killer (NK) cells. Unbiased transcriptomic screens showed increased NK cell activation in people with HIV, without B∗46, and simultaneous single-cell profiling of surface proteins and transcriptomes revealed a NK cell subset primed for increased responses in the absence of B∗46. These findings support a role for NK cells in HIV pathogenesis, revealed by the unique properties of the B∗46 allele common only in Asia. Published by Elsevier Inc.Entities:
Keywords: CD4 counts; CITE-seq; HLA; KIR; NK cells; RNA-seq; Thailand; acute HIV infection; cytotoxic T lymphocytes
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Year: 2022 PMID： 35841889 PMCID： PMC9380401 DOI： 10.1016/j.chom.2022.06.005
Source DB: PubMed Journal: Cell Host Microbe ISSN： 1931-3128 Impact factor: 31.316