HLA-B∗46 Associates with Rapid HIV Disease Progression in Asian Cohorts and Prominent Differences in NK Cell Phenotype

Overview

Journal Cell Host Microbe

Publisher Cell Press

Specialties Infectious Diseases
Microbiology

Date 2022 Jul 16

PMID 35841889

Authors

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

Eugene Kroon

Nittaya Phanuphak

Mark de Souza

Jintanat Ananworanich

Robert J OConnell

Merlin L Robb

Nelson L Michael

Sandhya Vasan

Rasmi Thomas

Affiliations

Soon will be listed here.

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.

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