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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
3' Untranslated Regions
-
Cell Cycle Proteins / genetics
-
Cell Cycle Proteins / metabolism
-
Cell Line
-
Gene Expression Regulation
-
Gene Products, tat / metabolism
-
HIV-1 / genetics
-
HIV-1 / physiology*
-
HeLa Cells
-
Histone Acetyltransferases / genetics
-
Histone Acetyltransferases / metabolism
-
Humans
-
Jurkat Cells
-
Leukocytes, Mononuclear / enzymology
-
Leukocytes, Mononuclear / virology*
-
MicroRNAs / genetics*
-
Oligonucleotide Array Sequence Analysis
-
RNA Interference*
-
RNA, Small Interfering / genetics
-
Ribonuclease III / genetics
-
Ribonuclease III / metabolism
-
Transcription Factors / genetics
-
Transcription Factors / metabolism
-
Transfection
-
Virus Latency
-
Virus Replication*
-
p300-CBP Transcription Factors
-
tat Gene Products, Human Immunodeficiency Virus
Substances
-
3' Untranslated Regions
-
Cell Cycle Proteins
-
Gene Products, tat
-
MicroRNAs
-
RNA, Small Interfering
-
Transcription Factors
-
tat Gene Products, Human Immunodeficiency Virus
-
Histone Acetyltransferases
-
p300-CBP Transcription Factors
-
p300-CBP-associated factor
-
DROSHA protein, human
-
Ribonuclease III