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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.

IRF-1 Is Required for Full NF-B Transcriptional Activity at the Human Immunodeficiency Virus Type 1 Long Terminal Repeat Enhancer

Marco Sgarbanti,^1, 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 Battistini^1*

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.