Kiene, MiriamMiriamKieneRethi, BenceBenceRethiJansson, MarianneMarianneJanssonDillon, StephanieStephanieDillonLee, EricEricLeeLantto, RebeckaRebeckaLanttoWilson, CaraCaraWilsonPöhlmann, StefanStefanPöhlmannChiodi, FrancescaFrancescaChiodi2019-07-092019-07-092014https://resolver.sub.uni-goettingen.de/purl?gro-2/60785Background Many HIV-2 and SIV isolates, as well as some HIV-1 strains, can use the orphan 7-transmembrane receptor GPR15 as co-receptor for efficient entry into host cells. GPR15 is expressed on central memory and effector memory CD4+ T cells in healthy individuals and a subset of these cells is susceptible to HIV-1 and SIV infection. However, it has not been determined whether GPR15 expression is altered in the context of HIV-1 infection. Results Here, we show that GPR15 expression in CD4+ T cells is markedly up-regulated in some HIV-1 infected individuals compared to the rest of the infected patients and to healthy controls. Infection of the PM1 T cell line with primary HIV-1 isolates was found to up-regulate GPR15 expression on the infected cells, indicating that viral components can induce GPR15 expression. Up-regulation of GPR15 expression on CD4+ T cells was induced by activation of Toll-like receptor 3 signalling via TIR-domain-containing adapter-inducing interferon-β (TRIF) and was more prominent on gut-homing compared to lymph node-homing CD4+ T cells. Conclusion These results suggest that infection-induced up-regulation of GPR15 expression could increase susceptibility of CD4+ T cells to HIV infection and target cell availability in the gut in some infected individuals.11enCC BY 4.0https://creativecommons.org/licenses/by/4.0journal_article10.1371/journal.pone.008819524558379https://resolver.sub.uni-goettingen.de/purl?gs-1/9997