Absence of DICER in monocytes and its regulation by HIV-1.
MicroRNAs (miRNAs) are a class of small RNA molecules that function to control gene expression and restrict viral replication in host cells. The production of miRNAs is believed to be dependent upon the DICER enzyme. Available evidence suggests that in T lymphocytes, HIV-1 can both suppress and co-opt the host's miRNA pathway for its own benefit. In this study, we examined the state of miRNA production in monocytes and macrophages as well as the consequences of viral infection upon the production of miRNA. Monocytes in general express low amounts of miRNA-related proteins, and DICER in particular could not be detected until after monocytes were differentiated into macrophages. In the case where HIV-1 was present prior to differentiation, the expression of DICER was suppressed. MicroRNA chip results for RNA isolated from transfected and treated cells indicated that a drop in miRNA production coincided with DICER protein suppression in macrophages. We found that the expression of DICER in monocytes is restricted by miR-106a, but HIV-1 suppressed DICER expression via the viral gene Vpr. Additionally, analysis of miRNA expression in monocytes and macrophages revealed evidence that some miRNAs can be processed by both DICER and PIWIL4. Results presented here have implications for both the pathology of viral infections in macrophages and the biogenesis of miRNAs. First, HIV-1 suppresses the expression and function of DICER in macrophages via a previously unknown mechanism. Second, the presence of miRNAs in monocytes lacking DICER indicates that some miRNAs can be generated by proteins other than DICER.
Coley
William
W
National Center for Biodefense and Infectious Diseases, Department of Molecular and Microbiology, George Mason University, Manassas, Virginia 20110, USA.
Van Duyne
Rachel
R
Carpio
Lawrence
L
Guendel
Irene
I
Kehn-Hall
Kylene
K
Chevalier
Sebastien
S
Narayanan
Aarthi
A
Luu
Truong
T
Lee
Norman
N
Klase
Zachary
Z
Kashanchi
Fatah
F
D060565:Argonaute Proteins; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D015852:Eukaryotic Initiation Factor-2 / Q000235:genetics / Q000378:metabolism; D039642:Eukaryotic Initiation Factors / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology / Q000201:enzymology* / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins; D043244:Ribonuclease III / Q000235:genetics / Q000378:metabolism*; D054325:vpr Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism
C115848:AGO1 protein, human; C466422:AGO2 protein, human; D060565:Argonaute Proteins; D015852:Eukaryotic Initiation Factor-2; D039642:Eukaryotic Initiation Factors; D035683:MicroRNAs; C556795:PIWIL4 protein, human; D011506:Proteins; D016601:RNA-Binding Proteins; D054325:vpr Gene Products, Human Immunodeficiency Virus; C514912:vpr protein, Human immunodeficiency virus 1; C517918:DROSHA protein, human; D043244:Ribonuclease III