Interleukin-10 inhibits HIV-1 LTR-directed gene expression in human macrophages through the induction of cyclin T1 proteolysis.
Regulation of HIV-1 replication in human monocytes/macrophages occurs at multiple levels including transcription of the proviral genome, which depends on virally encoded Tat protein. Interleukin-10 (IL-10), an anti-inflammatory cytokine which is up-regulated during disease progression of AIDS, has been reported to suppress HIV-1 replication in macrophages at a post-entry stage of the virus life cycle. Our previous studies have demonstrated that Tat function is regulated during the differentiation of monocyte-derived macrophages (MDMs) in a manner that correlates with the early induction and subsequent shut-off of its cellular cofactor cyclin T1. Here, we report that IL-10 down-regulates cyclin T1 expression through the induction of proteasome-mediated proteolysis in human macrophages. Using a reporter virus that is deficient in Tat function, we also demonstrate that IL-10 inhibits HIV-1 gene expression in a Tat-dependent manner. Together, these results suggest that the down-regulation of cyclin T1, and consequently Tat function, contributes to the suppressive effect of IL-10 on HIV-1 replication in human macrophages.
Wang
Yan
Y
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, One Baylor Plaza, Houston, TX 77030, USA.
Rice
Andrew P
AP
D001483:Base Sequence; D002454:Cell Differentiation; D056906:Cyclin T; D016213:Cyclins / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D016325:HIV Long Terminal Repeat / Q000187:drug effects* / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics* / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D016753:Interleukin-10 / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects
C503684:CCNT1 protein, human; D056906:Cyclin T; D016213:Cyclins; D012333:RNA, Messenger; D016753:Interleukin-10; D046988:Proteasome Endopeptidase Complex