IRF-1 is required for full NF-kappaB transcriptional activity at the human immunodeficiency virus type 1 long terminal repeat enhancer.
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.
Sgarbanti
Marco
M
Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, Viale Regina Elena, 299, Rome 00161, Italy.
Remoli
Anna L
AL
Marsili
Giulia
G
Ridolfi
Barbara
B
Borsetti
Alessandra
A
Perrotti
Edvige
E
Orsatti
Roberto
R
Ilari
Ramona
R
Sernicola
Leonardo
L
Stellacci
Emilia
E
Ensoli
Barbara
B
Battistini
Angela
A
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
D050856:Interferon Regulatory Factor-1; D016328:NF-kappa B