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Published Online February 22, 2007
Science DOI: 10.1126/science.1136319

Reports

Submitted on October 16, 2006
Accepted on February 13, 2007

Suppression of MicroRNA-Silencing Pathway by HIV-1 During Virus Replication

Robinson Triboulet 1, Bernard Mari 2, Yea-Lih Lin 3, Christine Chable-Bessia 1, Yamina Bennasser 4, Kevin Lebrigand 2, Bruno Cardinaud 2, Thomas Maurin 2, Pascal Barbry 2, Vincent Baillat 5, Jacques Reynes 5, Pierre Corbeau 3, Kuan-Teh Jeang 4, Monsef Benkirane 1*

1 Laboratoire de Virologie Moléculaire, Institut de Génétique Humaine, Montpellier, France.
2 Institut de Pharmacologie Moléculaire et Cellulaire, UMR6097 CNRS/UNSA, Sophia Antipolis, France.
3 Laboratoire des Lentivirus et Transfert de Gènes, Institut de Génétique Humaine, Montpellier, France.
4 Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
5 Service des Maladies Infectieuses et Tropicales, Hôpital Gui de Chauliac, Montpellier, France.

* To whom correspondence should be addressed.
Monsef Benkirane , E-mail: bmonsef{at}igh.cnrs.fr

MicroRNAs (miRNAs) are single-stranded noncoding RNAs of 19 to 25 nucleotides that function as gene regulators and in host cell defense against both RNA and DNA viruses. We provide evidence for a physiological role of the miRNA-silencing machinery in controlling HIV-1 replication. Type III RNAses Dicer and Drosha, responsible for miRNA processing, inhibited virus replication both in peripheral blood mononuclear cells (PBMCs) from HIV-1 infected donors and in latently infected cells. In turn, HIV-1 actively suppressed the expression of the polycistronic microRNA cluster miR-17/92. This suppression was found to be required for efficient viral replication and was dependent on the histone acetyltransferase Tat cofactor PCAF. Our results highlight the involvement of the miRNA-silencing pathway in HIV-1 replication and latency.


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Science. ISSN 0036-8075 (print), 1095-9203 (online)