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 journalArticlepeer-review

6 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 languageEnglish
Pages (from-to)1173-1185.e8
JournalCell Host and Microbe
Volume30
Issue number8
DOIs
StatePublished - 10 Aug 2022
Externally publishedYes

Keywords

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

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