title: IRF-1 is required for full NF-kappaB transcriptional activity at the human immunodeficiency virus type 1 long terminal repeat enhancer.
abstract: Human immunodeficiency virus type 1 (HIV-1) gene expression is controlled by a complex interplay between viral and host factors. We have previously shown that interferon-regulatory factor 1 (IRF-1) is stimulated early after HIV-1 infection and regulates promoter transcriptional activity even in the absence of the viral transactivator Tat. In this work we demonstrate that IRF-1 is also required for full NF-kappaB transcriptional activity. We provide evidence that IRF-1 and NF-kappaB form a functional complex at the long terminal repeat (LTR) kappaB sites, which is abolished by specific mutations in the two adjacent kappaB sites in the enhancer region. Silencing IRF-1 with small interfering RNA resulted in impaired NF-kappaB-mediated transcriptional activity and in repressed HIV-1 transcription early in de novo-infected T cells. These data indicate that in early phases of HIV-1 infection or during virus reactivation from latency, when the viral transactivator is absent or present at very low levels, IRF-1 is an additional component of the p50/p65 heterodimer binding the LTR enhancer, absolutely required for efficient HIV-1 replication.
authors.affiliation: Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, Viale Regina Elena, 299, Rome 00161, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Sgarbanti
authors.forename: Anna L
authors.initials: AL
authors.lastname: Remoli
authors.forename: Giulia
authors.initials: G
authors.lastname: Marsili
authors.forename: Barbara
authors.initials: B
authors.lastname: Ridolfi
authors.forename: Alessandra
authors.initials: A
authors.lastname: Borsetti
authors.forename: Edvige
authors.initials: E
authors.lastname: Perrotti
authors.forename: Roberto
authors.initials: R
authors.lastname: Orsatti
authors.forename: Ramona
authors.initials: R
authors.lastname: Ilari
authors.forename: Leonardo
authors.initials: L
authors.lastname: Sernicola
authors.forename: Emilia
authors.initials: E
authors.lastname: Stellacci
authors.forename: Barbara
authors.initials: B
authors.lastname: Ensoli
authors.forename: Angela
authors.initials: A
authors.lastname: Battistini
mesh_terms: D001665:Binding Sites; D002460:Cell Line; D024202:Electrophoretic Mobility Shift Assay; D020868:Gene Silencing; D016322:HIV Enhancer / Q000235:genetics*; D016325:HIV Long Terminal Repeat / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D047468:Immunoprecipitation; D050856:Interferon Regulatory Factor-1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D017354:Point Mutation; D011485:Protein Binding; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000821:virology
chemical_list: D050856:Interferon Regulatory Factor-1; D016328:NF-kappa B