Suppression of microRNA-silencing pathway by HIV-1 during virus replication.
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.
Triboulet
Robinson
R
Laboratoire de Virologie Moléculaire, Institut de Génétique Humaine, Montpellier, France.
Mari
Bernard
B
Lin
Yea-Lih
YL
Chable-Bessia
Christine
C
Bennasser
Yamina
Y
Lebrigand
Kevin
K
Cardinaud
Bruno
B
Maurin
Thomas
T
Barbry
Pascal
P
Baillat
Vincent
V
Reynes
Jacques
J
Corbeau
Pierre
P
Jeang
Kuan-Teh
KT
Benkirane
Monsef
M
D020413:3' Untranslated Regions; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D005786:Gene Expression Regulation; D015696:Gene Products, tat / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006367:HeLa Cells; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D007963:Leukocytes, Mononuclear / Q000201:enzymology / Q000821:virology*; D035683:MicroRNAs / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D043244:Ribonuclease III / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D017735:Virus Latency; D014779:Virus Replication; D050880:p300-CBP Transcription Factors; D054322:tat Gene Products, Human Immunodeficiency Virus; D000099224:p300-CBP-Associated Factor
D020413:3' Untranslated Regions; D018797:Cell Cycle Proteins; D015696:Gene Products, tat; D051548:Histone Acetyltransferases; D035683:MicroRNAs; D034741:RNA, Small Interfering; D043244:Ribonuclease III; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D054322:tat Gene Products, Human Immunodeficiency Virus; D000099224:p300-CBP-Associated Factor; C517918:DROSHA protein, human