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MicroRNAs (miRNAs) are single-stranded noncoding RNAs of 19to 25 nucleotides that function as gene regulators and as ahost cell defense against both RNA and DNA viruses. We provideevidence for a physiological role of the miRNA-silencing machineryin controlling HIV-1 replication. Type III RNAses Dicer andDrosha, responsible for miRNA processing, inhibited virus replicationboth in peripheral blood mononuclear cells from HIV-1–infecteddonors and in latently infected cells. In turn, HIV-1 activelysuppressed the expression of the polycistronic miRNA clustermiR-17/92. This suppression was found to be required for efficientviral replication and was dependent on the histone acetyltransferaseTat cofactor PCAF. Our results highlight the involvement ofthe 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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