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.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
APA Citation
Meltzer, B., Dabbagh, D., Guo, J., Kashanchi, F., Tyagi, M., & Wu, Y. (2018). Tat controls transcriptional persistence of unintegrated HIV genome in primary human macrophages.. Virology, 518 (). http://dx.doi.org/10.1016/j.virol.2018.03.006
Peer Reviewed
1
Open Access
1
Comments
Reproduced with permission of Elsevier B.V. Virology