Circulating integrin α4β7+ CD4 T cells are enriched for proliferative transcriptional programs in HIV infection

Yashavanth S. Lakshmanappa, Jamin W. Roh, Niharika N. Rane, Ashok R. Dinasarapu, Daphne D. Tran, Vijayakumar Velu, Anandi N. Sheth, Igho Ofotokun, Rama R. Amara, Colleen F. Kelley, Elaine Waetjen, Smita S. Iyer

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

HIV preferentially infects α4β7+ CD4 T cells, forming latent reservoirs that contribute to HIV persistence during antiretroviral therapy. However, the properties of α4β7+ CD4 T cells in blood and mucosal compartments remain understudied. Employing two distinct models of HIV infection, HIV-infected humans and simian–human immunodeficiency virus (SHIV)-infected rhesus macaques, we show that α4β7+ CD4 T cells in blood are enriched for genes regulating cell cycle progression and cellular metabolism. Unlike their circulating counterparts, rectal α4β7+ CD4 T cells exhibited a core tissue-residency gene expression program. These features were conserved across primate species, indicating that the environment influences memory T-cell transcriptional networks. Our findings provide an important molecular foundation for understanding the role of α4β7 in HIV infection.

Original languageEnglish (US)
Pages (from-to)2257-2270
Number of pages14
JournalFEBS Letters
Volume595
Issue number17
DOIs
StatePublished - Sep 2021

Keywords

  • HIV
  • integrin α4
  • rectal mucosa
  • susceptibility
  • tissue resident memory T cells
  • β7 CD4 T cells

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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