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Biology 2012, 1(1), 94-115; doi:10.3390/biology1010094
Review

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

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Received: 15 May 2012; in revised form: 7 June 2012 / Accepted: 11 June 2012 / Published: 15 June 2012
(This article belongs to the Special Issue Structural and Molecular Biology of HIV)
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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.
Keywords: P-TEFb; HIV-1; Tat; T-loop phosphorylation; Cyclin T1; miRNA P-TEFb; HIV-1; Tat; T-loop phosphorylation; Cyclin T1; miRNA
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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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.

AMA Style

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

Chicago/Turabian Style

Ramakrishnan, Rajesh; Chiang, Karen; Liu, Hongbing; Budhiraja, Sona; Donahue, Hart; Rice, Andrew P. 2012. "Making a Short Story Long: Regulation of P-TEFb and HIV-1 Transcriptional Elongation in CD4+ T Lymphocytes and Macrophages." Biology 1, no. 1: 94-115.



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