title: Blimp-1, an intrinsic factor that represses HIV-1 proviral transcription in memory CD4+ T cells.
abstract: CD4(+) T cell subsets differentially support HIV-1 replication. For example, quiescent CD4(+) memory T cells are susceptible to HIV-1 infection but do not support robust HIV-1 transcription and have been implicated as the primary reservoir of latent HIV-1. T cell transcription factors that regulate maturation potentially limit HIV-1 transcription and mediate the establishment and maintenance of HIV-1 latency. We report that B lymphocyte-induced maturation protein-1 (Blimp-1), a critical regulator of B and T cell differentiation, is highly expressed in memory CD4(+) T cells compared with naive CD4(+) T cells and represses basal and Tat-mediated HIV-1 transcription. Blimp-1 binds an IFN-stimulated response element within HIV-1 provirus, and it is displaced following T cell activation. Reduction of Blimp-1 in infected primary T cells including CD4(+) memory T cells increases RNA polymerase II processivity, histone acetylation, and baseline HIV-1 transcription. Therefore, the transcriptional repressor, Blimp-1, is an intrinsic factor that predisposes CD4(+) memory T cells to latent HIV-1 infection.
authors.affiliation: Section of Infectious Diseases, Department of Medicine, Boston University School of Medicine, Boston, MA 02118; Graduate Program in Molecular and Translational Medicine, Boston University School of Medicine, Boston, MA 02118;
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kaczmarek Michaels
authors.affiliation: Stowers Institute for Medical Research, Kansas City, MO 64110;
authors.forename: Malini
authors.initials: M
authors.lastname: Natarajan
authors.affiliation: Ragon Institute of MGH, MIT and Harvard University, Boston, MA 02139; and.
authors.forename: Zelda
authors.initials: Z
authors.lastname: Euler
authors.affiliation: Ragon Institute of MGH, MIT and Harvard University, Boston, MA 02139; and.
authors.forename: Galit
authors.initials: G
authors.lastname: Alter
authors.affiliation: Department of Microbiology, Boston University School of Medicine, Boston, MA 02118.
authors.forename: Gregory
authors.initials: G
authors.lastname: Viglianti
authors.affiliation: Section of Infectious Diseases, Department of Medicine, Boston University School of Medicine, Boston, MA 02118; Graduate Program in Molecular and Translational Medicine, Boston University School of Medicine, Boston, MA 02118; Department of Microbiology, Boston University School of Medicine, Boston, MA 02118 andrew.henderson@bmc.org.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Henderson
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000821:virology*; D002460:Cell Line; D015870:Gene Expression; D015967:Gene Expression Regulation, Viral; D015658:HIV Infections / Q000276:immunology / Q000821:virology*; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D008954:Models, Biological; D000074462:Positive Regulatory Domain I-Binding Factor 1; D011485:Protein Binding; D011533:Proviruses / Q000235:genetics* / Q000276:immunology; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D012097:Repressor Proteins; C087042:PRDM1 protein, human; D000074462:Positive Regulatory Domain I-Binding Factor 1