Small Interfering RNAs against the TAR RNA Binding Protein, TRBP, a Dicer Cofactor, Inhibit Human Immunodeficiency Virus Type 1 Long Terminal Repeat Expression and Viral Production

Helen S. Christensen; Aïcha Daher; Kaitlin J. Soye; Lisa B. Frankel; Marina R. Alexander; Sébastien Lainé; Sylvie Bannwarth; Chi L. Ong; Sean W. L. Chung; Shahan M. Campbell; Damian F. J. Purcell; Anne Gatignol

doi:10.1128/JVI.01511-06

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Small Interfering RNAs against the TAR RNA Binding Protein, TRBP, a Dicer Cofactor, Inhibit Human Immunodeficiency Virus Type 1 Long Terminal Repeat Expression and Viral Production

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Small Interfering RNAs against the TAR RNA Binding Protein, TRBP, a Dicer Cofactor, Inhibit Human Immunodeficiency Virus Type 1 Long Terminal Repeat Expression and Viral Production

Helen S. Christensen, Aïcha Daher, Kaitlin J. Soye, Lisa B. Frankel, Marina R. Alexander, Sébastien Lainé, Sylvie Bannwarth, Chi L. Ong, Sean W. L. Chung, Shahan M. Campbell, …

Journal of virology, Vol.81(10), pp.5121-5131

01/05/2007

DOI: https://doi.org/10.1128/JVI.01511-06

PMID: 17360756

Résumé

Genome and Regulation of Viral Gene Expression

RNA interference (RNAi) is now widely used for gene silencing in mammalian cells. The mechanism uses the RNA-induced silencing complex, in which Dicer, Ago2, and the human immunodeficiency virus type 1 (HIV-1) TAR RNA binding protein (TRBP) are the main components. TRBP is a protein that increases HIV-1 expression and replication by inhibition of the interferon-induced protein kinase PKR and by increasing translation of viral mRNA. After HIV infection, TRBP could restrict the viral RNA through its activity in RNAi or could contribute more to the enhancement of viral replication. To determine which function will be predominant in the virological context, we analyzed whether the inhibition of its expression could enhance or decrease HIV replication. We have generated small interfering RNAs (siRNAs) against TRBP and found that they decrease HIV-1 long terminal repeat (LTR) basal expression 2-fold, and the LTR Tat transactivated level up to 10-fold. In the context of HIV replication, siRNAs against TRBP decrease the expression of viral genes and inhibit viral production up to fivefold. The moderate increase in PKR expression and activation indicates that it contributes partially to viral gene inhibition. The moderate decrease in micro-RNA (miRNA) biogenesis by TRBP siRNAs suggests that in the context of HIV replication, TRBP functions other than RNAi are predominant. In addition, siRNAs against Dicer decrease viral production twofold and impede miRNA biogenesis. These results suggest that, in the context of HIV replication, TRBP contributes mainly to the enhancement of virus production and that Dicer does not mediate HIV restriction by RNAi.

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Titre: Small Interfering RNAs against the TAR RNA Binding Protein, TRBP, a Dicer Cofactor, Inhibit Human Immunodeficiency Virus Type 1 Long Terminal Repeat Expression and Viral Production
Créateurs - sans rôle: Helen S. Christensen - Department of Microbiology and Immunology, University of Melbourne, Parkville, Australia, Virus-Cell Interactions Laboratory, Lady Davis Institute for Medical Research, Departments of Microbiology and Immunology, Experimental Medicine, McGill University, Montréal, Québec, Canada
Aïcha Daher - Department of Microbiology and Immunology, University of Melbourne, Parkville, Australia, Virus-Cell Interactions Laboratory, Lady Davis Institute for Medical Research, Departments of Microbiology and Immunology, Experimental Medicine, McGill University, Montréal, Québec, Canada
Kaitlin J. Soye - Department of Microbiology and Immunology, University of Melbourne, Parkville, Australia, Virus-Cell Interactions Laboratory, Lady Davis Institute for Medical Research, Departments of Microbiology and Immunology, Experimental Medicine, McGill University, Montréal, Québec, Canada
Lisa B. Frankel - Department of Microbiology and Immunology, University of Melbourne, Parkville, Australia, Virus-Cell Interactions Laboratory, Lady Davis Institute for Medical Research, Departments of Microbiology and Immunology, Experimental Medicine, McGill University, Montréal, Québec, Canada
Marina R. Alexander - Department of Microbiology and Immunology, University of Melbourne, Parkville, Australia, Virus-Cell Interactions Laboratory, Lady Davis Institute for Medical Research, Departments of Microbiology and Immunology, Experimental Medicine, McGill University, Montréal, Québec, Canada
Sébastien Lainé - Department of Microbiology and Immunology, University of Melbourne, Parkville, Australia, Virus-Cell Interactions Laboratory, Lady Davis Institute for Medical Research, Departments of Microbiology and Immunology, Experimental Medicine, McGill University, Montréal, Québec, Canada
Sylvie Bannwarth - Department of Microbiology and Immunology, University of Melbourne, Parkville, Australia, Virus-Cell Interactions Laboratory, Lady Davis Institute for Medical Research, Departments of Microbiology and Immunology, Experimental Medicine, McGill University, Montréal, Québec, Canada
Chi L. Ong - Department of Microbiology and Immunology, University of Melbourne, Parkville, Australia, Virus-Cell Interactions Laboratory, Lady Davis Institute for Medical Research, Departments of Microbiology and Immunology, Experimental Medicine, McGill University, Montréal, Québec, Canada
Sean W. L. Chung - Department of Microbiology and Immunology, University of Melbourne, Parkville, Australia, Virus-Cell Interactions Laboratory, Lady Davis Institute for Medical Research, Departments of Microbiology and Immunology, Experimental Medicine, McGill University, Montréal, Québec, Canada
Shahan M. Campbell - Department of Microbiology and Immunology, University of Melbourne, Parkville, Australia, Virus-Cell Interactions Laboratory, Lady Davis Institute for Medical Research, Departments of Microbiology and Immunology, Experimental Medicine, McGill University, Montréal, Québec, Canada
Damian F. J. Purcell - Department of Microbiology and Immunology, University of Melbourne, Parkville, Australia, Virus-Cell Interactions Laboratory, Lady Davis Institute for Medical Research, Departments of Microbiology and Immunology, Experimental Medicine, McGill University, Montréal, Québec, Canada
Anne Gatignol - Department of Microbiology and Immunology, University of Melbourne, Parkville, Australia, Virus-Cell Interactions Laboratory, Lady Davis Institute for Medical Research, Departments of Microbiology and Immunology, Experimental Medicine, McGill University, Montréal, Québec, Canada
Détails de publication: Journal of virology, Vol.81(10), pp.5121-5131
Éditeur: American Society for Microbiology
Nombre de pages: 11
Identifiants: 99141201109311
Unité académique: Institut de Recherche en Infectiologie de Montpellier - IRIM
Langue: English
Type de ressource: Journal article