title: Toll-like receptor 3 signalling up-regulates expression of the HIV co-receptor G-protein coupled receptor 15 on human CD4+ T cells.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Virology, Hannover Medical School, Hannover, Germany ; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Miriam
authors.initials: M
authors.lastname: Kiene
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Bence
authors.initials: B
authors.lastname: Rethi
authors.affiliation: Department of Laboratory Medicine, Lund University, Lund, Sweden.
authors.forename: Marianne
authors.initials: M
authors.lastname: Jansson
authors.affiliation: Division of Infectious Diseases, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States of America.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Dillon
authors.affiliation: Division of Infectious Diseases, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States of America.
authors.forename: Eric
authors.initials: E
authors.lastname: Lee
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Rebecka
authors.initials: R
authors.lastname: Lantto
authors.affiliation: Division of Infectious Diseases, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States of America.
authors.forename: Cara
authors.initials: C
authors.lastname: Wilson
authors.affiliation: Infection Biology Unit, German Primate Center, Göttingen, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Pöhlmann
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Francesca
authors.initials: F
authors.lastname: Chiodi
mesh_terms: D000328:Adult; D018941:Antigens, CD19 / Q000378:metabolism; D001706:Biopsy; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000821:virology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D002469:Cell Separation; D003106:Colon / Q000378:metabolism / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D007156:Immunologic Memory; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008297:Male; D008875:Middle Aged; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D018000:Receptors, Peptide / Q000378:metabolism*; D015398:Signal Transduction; D051196:Toll-Like Receptor 3 / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D018941:Antigens, CD19; C103539:GPR15 protein, human; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3