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Circulating integrin α4β7+ CD4 T cells are enriched for proliferative transcriptional programs in HIV infection
FEBS Letters  (IF4.124),  Pub Date : 2021-07-19, DOI: 10.1002/1873-3468.14163
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

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.