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Activation of Human Immunodeficiency Virus Transcription in T Cells Revisited: NF-?B p65 Stimulates Transcriptional Elongation

journal contribution
posted on 2023-06-08, 09:07 authored by Michelle WestMichelle West, Anthony D Lowe, Jonathan Karn
Human immunodeficiency virus type 1 (HIV-1) is able to establish a persistent latent infection during which the integrated provirus remains transcriptionally silent. Viral transcription is stimulated by NF-¿B, which is activated following the exposure of infected T cells to antigens or mitogens. Although it is commonly assumed that NF-¿B stimulates transcriptional initiation alone, we have found using RNase protection assays that, in addition to stimulating initiation, it can also stimulate elongation from the HIV-1 long terminal repeat. When either Jurkat or CCRF/CEM cells were activated by the mitogens phorbol myristate acetate and phytohemagglutinin, elongation, as measured by the proportion of full-length transcripts, increased two- to fourfold, even in the absence of Tat. Transfection of T cells with plasmids carrying the different subunits of NF-¿B demonstrated that the activation of transcriptional elongation is mediated specifically by the p65 subunit. It seems likely that initiation is activated because of NF-¿B's ability to disrupt chromatin structures through the recruitment of histone acetyltransferases. To test whether p65 could stimulate elongation under conditions where it did not affect histone acetylation, cells were treated with the histone deacetylase inhibitor trichostatin A. Remarkably, addition of p65 to the trichostatin A-treated cell lines resulted in a dramatic increase in transcription elongation, reaching levels equivalent to those observed in the presence of Tat. We suggest that the activation of elongation by NF-¿B p65 involves a distinct biochemical mechanism, probably the activation of carboxyl-terminal domain kinases at the promoter.

History

Publication status

  • Published

Journal

Journal of Virology

ISSN

0022-538X

Publisher

American Society for Microbiology

Issue

18

Volume

75

Page range

8524-8537

Pages

14.0

Department affiliated with

  • Biochemistry Publications

Notes

95% of the data in this paper was generated by West as a post-doc in the Karn lab.

Full text available

  • No

Peer reviewed?

  • Yes

Legacy Posted Date

2012-02-06

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