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Key Players in HIV-1 Transcriptional Regulation: Targets for a Functional Cure

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HIV-1 Proviral Transcription and Latency in the New Era

Department of Microbiology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Viruses 2020, 12(5), 555; https://doi.org/10.3390/v12050555
Received: 13 April 2020 / Revised: 6 May 2020 / Accepted: 12 May 2020 / Published: 18 May 2020
(This article belongs to the Special Issue HIV-1 Transcription Regulation)
Three decades of extensive work in the HIV field have revealed key viral and host cell factors controlling proviral transcription. Various models of transcriptional regulation have emerged based on the collective information from in vitro assays and work in both immortalized and primary cell-based models. Here, we provide a recount of the past and current literature, highlight key regulatory aspects, and further describe potential limitations of previous studies. We particularly delve into critical steps of HIV gene expression including the role of the integration site, nucleosome positioning and epigenomics, and the transition from initiation to pausing and pause release. We also discuss open questions in the field concerning the generality of previous regulatory models to the control of HIV transcription in patients under suppressive therapy, including the role of the heterogeneous integration landscape, clonal expansion, and bottlenecks to eradicate viral persistence. Finally, we propose that building upon previous discoveries and improved or yet-to-be discovered technologies will unravel molecular mechanisms of latency establishment and reactivation in a “new era”.
Keywords: HIV-1; provirus; persistence; cure; integration; transcription; ART; latency; latent reservoir; epigenomics HIV-1; provirus; persistence; cure; integration; transcription; ART; latency; latent reservoir; epigenomics
MDPI and ACS Style

Shukla, A.; Ramirez, N.-G.; D’Orso, I. HIV-1 Proviral Transcription and Latency in the New Era. Viruses 2020, 12, 555.

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