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Journal of Virology, April 2008, p. 3632-3641, Vol. 82, No. 7
0022-538X/08/$08.00+0 doi:10.1128/JVI.00599-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.
B Transcriptional Activity at the Human Immunodeficiency Virus Type 1 Long Terminal Repeat Enhancer
Anna L. Remoli,1,
Giulia Marsili,1,
Barbara Ridolfi,2
Alessandra Borsetti,2
Edvige Perrotti,1
Roberto Orsatti,1
Ramona Ilari,1
Leonardo Sernicola,2
Emilia Stellacci,1
Barbara Ensoli,2 and
Angela Battistini1*
Department of Infectious, Parasitic and Immune-Mediated Diseases,1 National AIDS Centre, Istituto Superiore di Sanità, Viale Regina Elena, 299, Rome 00161, Italy2
Received 20 March 2007/ Accepted 9 January 2008
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-
B transcriptional activity. We provide evidence that IRF-1 and NF-
B form a functional complex at the long terminal repeat (LTR)
B sites, which is abolished by specific mutations in the two adjacent
B sites in the enhancer region. Silencing IRF-1 with small interfering RNA resulted in impaired NF-
B-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.
Published ahead of print on 23 January 2008.
These authors contributed equally to this work.
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