RNA interference directed to CDK2 inhibits HIV-1 transcription.
We previously reported that cell cycle-dependent kinase 2 (CDK2) is required for human immunodeficiency virus-1 (HIV-1) Tat-dependent transcription in vitro. In the present study, CDK2-specific RNA interference in cultured HEK293T cells inhibited CDK2 expression and Tat-induced HIV-1 transcription from non-integrated HIV-1 promoter but not basal HIV-1 transcription or transcription from CMV or beta-actin promoters. Also, CDK2-specific RNA interference inhibited Tat-induced transcription from the integrated HIV-1 promoter in HeLa-CD4-LTR-beta-gal cells and potently blocked TNFalpha-induced HIV-1 viral replication in OM10.1 cells. CDK2-specific RNA interference did not have an effect on cell cycle progression, but it augmented TNFalpha-induced apoptosis of OM10.1 cells. Our results indicate that CDK2 participates in Tat-mediated HIV-1 transcription and may serve as a potential therapeutic target.
Ammosova
Tatyana
T
Center for Sickle Cell Disease, Howard University College of Medicine, NW, Washington, DC 20059, USA.
Berro
Reem
R
Kashanchi
Fatah
F
Nekhai
Sergei
S
D000199:Actins / Q000235:genetics; D017209:Apoptosis; D051357:Cyclin-Dependent Kinase 2 / Q000235:genetics* / Q000502:physiology*; D003587:Cytomegalovirus / Q000235:genetics; D015696:Gene Products, tat / Q000378:metabolism*; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D034741:RNA, Small Interfering; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D014779:Virus Replication; D054322:tat Gene Products, Human Immunodeficiency Virus
D000199:Actins; D015696:Gene Products, tat; D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha; D054322:tat Gene Products, Human Immunodeficiency Virus; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2