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Science 315 (5818): 1579-1582

Copyright © 2007 by the American Association for the Advancement of Science

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

Robinson Triboulet,1 Bernard Mari,3 Yea-Lih Lin,2 Christine Chable-Bessia,1 Yamina Bennasser,5 Kevin Lebrigand,3 Bruno Cardinaud,3 Thomas Maurin,3 Pascal Barbry,3 Vincent Baillat,4 Jacques Reynes,4 Pierre Corbeau,2 Kuan-Teh Jeang,5 Monsef Benkirane1*

Abstract: MicroRNAs (miRNAs) are single-stranded noncoding RNAs of 19 to 25 nucleotides that function as gene regulators and as a 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 from HIV-1–infected donors and in latently infected cells. In turn, HIV-1 actively suppressed the expression of the polycistronic miRNA 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.

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

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

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