title: The microRNA-9/B-lymphocyte-induced maturation protein-1/IL-2 axis is differentially regulated in progressive HIV infection.
abstract: The fine control of T-cell differentiation and its impact on HIV disease states is poorly understood. In this study, we demonstrate that B-lymphocyte-induced maturation protein-1 (Blimp-1/Prdm1) is highly expressed in CD4(+) T cells from chronically HIV-infected (CHI) patients compared to cells from long-term nonprogressors or healthy controls. Stimulation through the T-cell receptor in the presence of IL-2 induces Blimp-1 protein expression. We show here that Blimp-1 levels are translationally regulated by microRNA-9 (miR-9). Overexpression of miR-9 induces Blimp-1 repression, restoring IL-2 secretion in CD4(+) T cells via reduction in the binding of Blimp-1 to the il-2 promoter. In CHI patients where IL-2 expression is reduced and there is generalized T-cell dysfunction, we show differential expression of both miR-9 and Blimp-1 in CD4(+) cells compared with levels in long-term nonprogressors. These data identify a novel miR-9/Blimp-1/IL-2 axis that is dysregulated in progressive HIV infection.
authors.affiliation: St Vincent's Centre for Applied Medical Research, Darlinghurst, NSW, Australia. nabila.seddiki@inserm.fr
authors.forename: Nabila
authors.initials: N
authors.lastname: Seddiki
authors.forename: Chansavath
authors.initials: C
authors.lastname: Phetsouphanh
authors.forename: Sanjay
authors.initials: S
authors.lastname: Swaminathan
authors.forename: Yin
authors.initials: Y
authors.lastname: Xu
authors.forename: Sudha
authors.initials: S
authors.lastname: Rao
authors.forename: Jasmine
authors.initials: J
authors.lastname: Li
authors.forename: Elissa L
authors.initials: EL
authors.lastname: Sutcliffe
authors.forename: Gareth
authors.initials: G
authors.lastname: Denyer
authors.forename: Robert
authors.initials: R
authors.lastname: Finlayson
authors.forename: Linda
authors.initials: L
authors.lastname: Gelgor
authors.forename: David A
authors.initials: DA
authors.lastname: Cooper
authors.forename: John
authors.initials: J
authors.lastname: Zaunders
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Kelleher
mesh_terms: D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D005260:Female; D015658:HIV Infections / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D019169:Jurkat Cells; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D000074462:Positive Regulatory Domain I-Binding Factor 1; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology; D055815:Young Adult
chemical_list: D007376:Interleukin-2; C541874:MIRN92 microRNA, human; D035683:MicroRNAs; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D011948:Receptors, Antigen, T-Cell; D012097:Repressor Proteins; C087042:PRDM1 protein, human; D000074462:Positive Regulatory Domain I-Binding Factor 1