Suppression of microRNA-silencing pathway by HIV-1 during virus replication

被引:502
作者
Triboulet, Robinson
Mari, Bernard
Lin, Yea-Lih
Chable-Bessia, Christine
Bennasser, Yamina
Lebrigand, Kevin
Cardinaud, Bruno
Maurin, Thomas
Barbry, Pascal
Baillat, Vincent
Reynes, Jacques
Corbeau, Pierre
Jeang, Kuan-Teh
Benkirane, Monsef [1 ]
机构
[1] Inst Genet Humaine, Mol Virol Lab, Montpellier, France
[2] Inst Genet Humaine, Lab Lentivirus & Transfert Genes, Montpellier, France
[3] UNSA, CNRS, UMR 6097, Inst Pharmacol Mol & Cellulaire, Sophia Antipolis, France
[4] Hop Gui de Chauliac, Serv Malad Infect & Trop, Montpellier, France
[5] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA
关键词
D O I
10.1126/science.1136319
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:1579 / 1582
页数:4
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