@article{17bc7813d7764542be23fb49df81dc32,
title = "HLA-B∗46 associates with rapid HIV disease progression in Asian cohorts and prominent differences in NK cell phenotype",
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.",
keywords = "CD4 counts, CITE-seq, HLA, KIR, NK cells, RNA-seq, Thailand, acute HIV infection, cytotoxic T lymphocytes",
author = "Li, \{Shuying S.\} and Andrew Hickey and Shida Shangguan and Ehrenberg, \{Philip K.\} and Aviva Geretz and Lauryn Butler and Gautam Kundu and Richard Apps and Matthew Creegan and Clifford, \{Robert J.\} and Suteeraporn Pinyakorn and Eller, \{Leigh Anne\} and Pikunchai Luechai and Gilbert, \{Peter B.\} and Holtz, \{Timothy H.\} and Anupong Chitwarakorn and Carlo Sacdalan and Eug{\`e}ne Kroon and Nittaya Phanuphak and \{de Souza\}, Mark and Jintanat Ananworanich and O'Connell, \{Robert J.\} and Robb, \{Merlin L.\} and Michael, \{Nelson L.\} and Sandhya Vasan and Rasmi Thomas",
note = "Funding Information: We would like to thank the volunteers and staff of the RV152, RV254/SEARCH 010, BMCS, and RV217 cohorts. We thank Dr. Denise Hsu, MHRP for helpful comments. The views expressed are those of the authors and should not be construed to represent the positions or views of the US Army or the US Department of Defense (DOD), the US Centers for Disease Control and Prevention, and/or the US Public Health Service and/or the US Government. This work was supported by a cooperative agreement (W81XWH-07-2-0067) between the Henry M. Jackson Foundation for the Advancement of Military Medicine , Inc., the DOD , and CDC /DHAP. This research was funded in part by the US National Institute of Allergy and Infectious Disease . Funding Information: We would like to thank the volunteers and staff of the RV152, RV254/SEARCH 010, BMCS, and RV217 cohorts. We thank Dr. Denise Hsu, MHRP for helpful comments. The views expressed are those of the authors and should not be construed to represent the positions or views of the US Army or the US Department of Defense (DOD), the US Centers for Disease Control and Prevention, and/or the US Public Health Service and/or the US Government. This work was supported by a cooperative agreement (W81XWH-07-2-0067) between the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. the DOD, and CDC/DHAP. This research was funded in part by the US National Institute of Allergy and Infectious Disease. The RV254/SEARCH 010 is supported by cooperative agreements (WW81XWH-18-2-0040) between the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. and the US Department of Defense (DOD); by an intramural grant from the Thai Red Cross AIDS Research Centre; and, in part, by the Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institute of Health (DAIDS, NIAID, NIH) (grant AAI20052001). We are grateful to the Thai Government Pharmaceutical Organization (GPO), ViiV Healthcare, Gilead Sciences, and Merck for providing the antiretroviral medications for this study. Material has been reviewed by the Walter Reed Army Institute of Research, and there is no objection to its presentation and/or publication. The investigators have adhered to the policies for protection of human subjects as prescribed in AR 70–25. Conceptualization, A.H. N.L.M. P.B.G. R.J.O. and R.T.; formal analysis and investigation, S.S.L. S.S. A.G. G.K. R.J.C. M.d.S. R.A. and R.T.; funding acquisition, N.L.M. S.V. and M.L.R.; methodology, P.K.E. L.B. M.C. and M.d.S.; project administration and supervision, R.T.; resources, J.A. A.C. T.H.H. C.S. P.L. S.P. L.A.E. E.K. N.P. and S.V.; writing – original draft, S.S.L. S.S. A.H. and R.T.; writing – review \& editing, all authors. The authors declare no competing interests. Funding Information: The RV254/SEARCH 010 is supported by cooperative agreements ( WW81XWH-18-2-0040 ) between the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. and the US Department of Defense (DOD); by an intramural grant from the Thai Red Cross AIDS Research Centre ; and, in part, by the Division of AIDS , National Institute of Allergy and Infectious Diseases, National Institute of Health (DAIDS, NIAID, NIH ) (grant AAI20052001 ). We are grateful to the Thai Government Pharmaceutical Organization (GPO), ViiV Healthcare, Gilead Sciences, and Merck for providing the antiretroviral medications for this study. Material has been reviewed by the Walter Reed Army Institute of Research, and there is no objection to its presentation and/or publication. The investigators have adhered to the policies for protection of human subjects as prescribed in AR 70–25. Publisher Copyright: {\textcopyright} 2022",
year = "2022",
month = aug,
day = "10",
doi = "10.1016/j.chom.2022.06.005",
language = "English",
volume = "30",
pages = "1173--1185.E8",
journal = "Cell host \& microbe",
issn = "1931-3128",
publisher = "Cell Press",
number = "8",
}
SDG 3 Good Health and Well-being