HLA-B∗46 associates with rapid HIV disease progression in Asian cohorts and prominent differences in NK cell phenotype

Shuying S. Li; Andrew Hickey; Shida Shangguan; Philip K. Ehrenberg; Aviva Geretz; Lauryn Butler; Gautam Kundu; Richard Apps; Matthew Creegan; Robert J. Clifford; Suteeraporn Pinyakorn; Leigh Anne Eller; Pikunchai Luechai; Peter B. Gilbert; Timothy H. Holtz; Anupong Chitwarakorn; Carlo Sacdalan; Eugène Kroon; Nittaya Phanuphak; Mark de Souza; Jintanat Ananworanich; Robert J. O'Connell; Merlin L. Robb; Nelson L. Michael; Sandhya Vasan; Rasmi Thomas

doi:10.1016/j.chom.2022.06.005

HLA-B∗46 associates with rapid HIV disease progression in Asian cohorts and prominent differences in NK cell phenotype

Shuying S. Li, Andrew Hickey, Shida Shangguan, Philip K. Ehrenberg, Aviva Geretz, Lauryn Butler, Gautam Kundu, Richard Apps, Matthew Creegan, Robert J. Clifford, Suteeraporn Pinyakorn, Leigh Anne Eller, Pikunchai Luechai, Peter B. Gilbert, Timothy H. Holtz, Anupong Chitwarakorn, Carlo Sacdalan, Eugène Kroon, Nittaya Phanuphak, Mark de SouzaJintanat Ananworanich, Robert J. O'Connell, Merlin L. Robb, Nelson L. Michael, Sandhya Vasan, Rasmi Thomas^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

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.

Original language	English
Pages (from-to)	1173-1185.e8
Journal	Cell Host and Microbe
Volume	30
Issue number	8
DOIs	https://doi.org/10.1016/j.chom.2022.06.005
State	Published - 10 Aug 2022
Externally published	Yes

Keywords

CD4 counts
CITE-seq
HLA
KIR
NK cells
RNA-seq
Thailand
acute HIV infection
cytotoxic T lymphocytes

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Li, S. S., Hickey, A., Shangguan, S., Ehrenberg, P. K., Geretz, A., Butler, L., Kundu, G., Apps, R., Creegan, M., Clifford, R. J., Pinyakorn, S., Eller, L. A., Luechai, P., Gilbert, P. B., Holtz, T. H., Chitwarakorn, A., Sacdalan, C., Kroon, E., Phanuphak, N., ... Thomas, R. (2022). HLA-B∗46 associates with rapid HIV disease progression in Asian cohorts and prominent differences in NK cell phenotype. Cell Host and Microbe, 30(8), 1173-1185.e8. https://doi.org/10.1016/j.chom.2022.06.005

@article{98ba83bdb7174dc78502d5175ddccc25,

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 = "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 and Microbe",

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Li, SS, Hickey, A, Shangguan, S, Ehrenberg, PK, Geretz, A, Butler, L, Kundu, G, Apps, R, Creegan, M, Clifford, RJ, Pinyakorn, S, Eller, LA, Luechai, P, Gilbert, PB, Holtz, TH, Chitwarakorn, A, Sacdalan, C, Kroon, E, Phanuphak, N, de Souza, M, Ananworanich, J, O'Connell, RJ, Robb, ML, Michael, NL, Vasan, S & Thomas, R 2022, 'HLA-B∗46 associates with rapid HIV disease progression in Asian cohorts and prominent differences in NK cell phenotype', Cell Host and Microbe, vol. 30, no. 8, pp. 1173-1185.e8. https://doi.org/10.1016/j.chom.2022.06.005

TY - JOUR

T1 - HLA-B∗46 associates with rapid HIV disease progression in Asian cohorts and prominent differences in NK cell phenotype

AU - Li, Shuying S.

AU - Hickey, Andrew

AU - Shangguan, Shida

AU - Ehrenberg, Philip K.

AU - Geretz, Aviva

AU - Butler, Lauryn

AU - Kundu, Gautam

AU - Apps, Richard

AU - Creegan, Matthew

AU - Clifford, Robert J.

AU - Pinyakorn, Suteeraporn

AU - Eller, Leigh Anne

AU - Luechai, Pikunchai

AU - Gilbert, Peter B.

AU - Holtz, Timothy H.

AU - Chitwarakorn, Anupong

AU - Sacdalan, Carlo

AU - Kroon, Eugène

AU - Phanuphak, Nittaya

AU - de Souza, Mark

AU - Ananworanich, Jintanat

AU - O'Connell, Robert J.

AU - Robb, Merlin L.

AU - Michael, Nelson L.

AU - Vasan, Sandhya

AU - Thomas, Rasmi

PY - 2022/8/10

Y1 - 2022/8/10

N2 - 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.

AB - 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.

KW - CD4 counts

KW - CITE-seq

KW - HLA

KW - KIR

KW - NK cells

KW - RNA-seq

KW - Thailand

KW - acute HIV infection

KW - cytotoxic T lymphocytes

UR - http://www.scopus.com/inward/record.url?scp=85135693686&partnerID=8YFLogxK

U2 - 10.1016/j.chom.2022.06.005

DO - 10.1016/j.chom.2022.06.005

M3 - Article

C2 - 35841889

AN - SCOPUS:85135693686

SN - 1931-3128

VL - 30

SP - 1173-1185.e8

JO - Cell Host and Microbe

JF - Cell Host and Microbe

IS - 8

ER -

HLA-B∗46 associates with rapid HIV disease progression in Asian cohorts and prominent differences in NK cell phenotype

Abstract

Keywords

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