Document Type

Journal Article

Publication Date

5-1-2018

Journal

Virology

Volume

518

Inclusive Pages

241-252

DOI

10.1016/j.virol.2018.03.006

Keywords

Cells, Cultured; DNA, Viral; HIV; Humans; Macrophages; Transcription, Genetic; tat Gene Products, Human Immunodeficiency Virus

Abstract

In HIV infected macrophages, a large population of viral genomes persists as the unintegrated form (uDNA) that is transcriptionally active. However, how this transcriptional activity is controlled remains unclear. In this report, we investigated whether Tat, the viral transactivator of transcription, is involved in uDNA transcription. We demonstrate that de novo Tat activity is generated from uDNA, and this uDNA-derived Tat (uTat) transactivates the uDNA LTR. In addition, uTat is required for the transcriptional persistence of uDNA that is assembled into repressive episomal minichromatin. In the absence of uTat, uDNA minichromatin is gradually silenced, but remains highly inducible by HDAC inhibitors (HDACi). Therefore, functionally, uTat antagonizes uDNA minichromatin repression to maintain persistent viral transcription in macrophages. uTat-mediated viral persistence may establish a viral reservoir in macrophages where uDNA were found to persist.

Comments

Reproduced with permission of Elsevier B.V. Virology

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

Peer Reviewed

1

Open Access

1

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