Next Article in Journal / Special Issue
Dynamic Post-Transcriptional Regulation of HIV-1 Gene Expression
Previous Article in Journal / Special Issue
Higher Desolvation Energy Reduces Molecular Recognition in Multi-Drug Resistant HIV-1 Protease
Article Menu

Export Article

Open AccessReview
Biology 2012, 1(1), 94-115; https://doi.org/10.3390/biology1010094

Making a Short Story Long: Regulation of P-TEFb and HIV-1 Transcriptional Elongation in CD4+ T Lymphocytes and Macrophages

1
Department of Molecular Virology & Microbiology, Baylor College of Medicine, Houston, TX 77030, USA
2
Interdepartmental Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, TX 77030, USA
*
Author to whom correspondence should be addressed.
Received: 15 May 2012 / Revised: 7 June 2012 / Accepted: 11 June 2012 / Published: 15 June 2012
(This article belongs to the Special Issue Structural and Molecular Biology of HIV)
Full-Text   |   PDF [573 KB, uploaded 15 June 2012]   |  

Abstract

Productive transcription of the integrated HIV-1 provirus is restricted by cellular factors that inhibit RNA polymerase II elongation. The viral Tat protein overcomes this by recruiting a general elongation factor, P-TEFb, to the TAR RNA element that forms at the 5’ end of nascent viral transcripts. P-TEFb exists in multiple complexes in cells, and its core consists of a kinase, Cdk9, and a regulatory subunit, either Cyclin T1 or Cyclin T2. Tat binds directly to Cyclin T1 and thereby targets the Cyclin T1/P-TEFb complex that phosphorylates the CTD of RNA polymerase II and the negative factors that inhibit elongation, resulting in efficient transcriptional elongation. P-TEFb is tightly regulated in cells infected by HIV-1—CD4+ T lymphocytes and monocytes/macrophages. A number of mechanisms have been identified that inhibit P-TEFb in resting CD4+ T lymphocytes and monocytes, including miRNAs that repress Cyclin T1 protein expression and dephosphorylation of residue Thr186 in the Cdk9 T-loop. These repressive mechanisms are overcome upon T cell activation and macrophage differentiation when the permissivity for HIV-1 replication is greatly increased. This review will summarize what is currently known about mechanisms that regulate P-TEFb and how this regulation impacts HIV-1 replication and latency. View Full-Text
Keywords: P-TEFb; HIV-1; Tat; T-loop phosphorylation; Cyclin T1; miRNA P-TEFb; HIV-1; Tat; T-loop phosphorylation; Cyclin T1; miRNA
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).
SciFeed

Share & Cite This Article

MDPI and ACS Style

Ramakrishnan, R.; Chiang, K.; Liu, H.; Budhiraja, S.; Donahue, H.; Rice, A.P. Making a Short Story Long: Regulation of P-TEFb and HIV-1 Transcriptional Elongation in CD4+ T Lymphocytes and Macrophages. Biology 2012, 1, 94-115.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Biology EISSN 2079-7737 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top