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Journal of Virology, December 2001, p. 11336-11343, Vol. 75, No. 23
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.23.11336-11343.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Induction of TAK (Cyclin T1/P-TEFb) in Purified Resting CD4+ T Lymphocytes by Combination of Cytokines

Romi Ghose,dagger Li-Ying Liou, Christine H. Herrmann, and Andrew P. Rice*

Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas 77030

Received 16 May 2001/Accepted 3 August 2001

Combinations of cytokines are known to reactivate transcription and replication of latent human immunodeficiency virus type 1 (HIV-1) proviruses in resting CD4+ T lymphocytes isolated from infected individuals. Transcription of the HIV-1 provirus by RNA polymerase II is strongly stimulated by the viral Tat protein. Tat function is mediated by a cellular protein kinase known as TAK (cyclin T1/P-TEFb) that is composed of Cdk9 and cyclin T1. We have found that treatment of peripheral blood lymphocytes and purified resting CD4+ T lymphocytes with the combination of interleukin-2 (IL-2), IL-6, and tumor necrosis factor alpha resulted in an increase in Cdk9 and cyclin T1 protein levels and an increase in TAK enzymatic activity. The cytokine induction of TAK in resting CD4+ T lymphocytes did not appear to require proliferation of lymphocytes. These results suggest that induction of TAK by cytokines secreted in the microenvironment of lymphoid tissue may be involved in the reactivation of HIV-1 in CD4+ T lymphocytes harboring a latent provirus.


* Corresponding author. Mailing address: Department of Molecular Virology and Microbiology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030. Phone: (713) 798-5774. Fax: (713) 798-3490. E-mail: arice{at}bcm.tmc.edu.

dagger Present address: Amphioxus Cell Technologies, Houston, TX 77082.


Journal of Virology, December 2001, p. 11336-11343, Vol. 75, No. 23
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.23.11336-11343.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.



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