miR-198 inhibits HIV-1 gene expression and replication in monocytes and its mechanism of action appears to involve repression of cyclin T1.
Cyclin T1 is a regulatory subunit of a general RNA polymerase II elongation factor known as P-TEFb. Cyclin T1 is also required for Tat transactivation of HIV-1 LTR-directed gene expression. Translation of Cyclin T1 mRNA has been shown to be repressed in human monocytes, and this repression is relieved when cells differentiate to macrophages. We identified miR-198 as a microRNA (miRNA) that is strongly down-regulated when monocytes are induced to differentiate. Ectopic expression of miR-198 in tissue culture cells reduced Cyclin T1 protein expression, and plasmid reporter assays verified miR-198 target sequences in the 3' untranslated region (3'UTR) of Cyclin T1 mRNA. Cyclin T1 protein levels increased when an inhibitor of miR-198 was transfected into primary monocytes, and overexpression of miR-198 in primary monocytes repressed the normal up-regulation of Cyclin T1 during differentiation. Expression of an HIV-1 proviral plasmid and HIV-1 replication were repressed in a monocytic cell line upon overexpression of miR-198. Our data indicate that miR-198 functions to restrict HIV-1 replication in monocytes, and its mechanism of action appears to involve repression of Cyclin T1 expression.
Sung
Tzu-Ling
TL
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, United States of America.
Rice
Andrew P
AP
D020413:3' Untranslated Regions / Q000187:drug effects; D002454:Cell Differentiation; D002460:Cell Line; D056906:Cyclin T; D016213:Cyclins / Q000187:drug effects*; D015536:Down-Regulation; D015658:HIV Infections / Q000235:genetics; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D008264:Macrophages / Q000821:virology; D035683:MicroRNAs / Q000502:physiology*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism / Q000821:virology*; D012333:RNA, Messenger / Q000378:metabolism; D014779:Virus Replication / Q000235:genetics
D020413:3' Untranslated Regions; C503684:CCNT1 protein, human; D056906:Cyclin T; D016213:Cyclins; C535221:MIRN198 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger