HIV-1 proviral transcription and latency in the new era

Ashutosh Shukla, Nora Guadalupe P. Ramirez, Iván D'Orso

Research output: Contribution to journalReview articlepeer-review

2 Scopus citations

Abstract

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".

Original languageEnglish (US)
Article numberv12050555
JournalViruses
Volume12
Issue number5
DOIs
StatePublished - May 2020

Keywords

  • ART
  • Cure
  • Epigenomics
  • HIV-1
  • Integration
  • Latency
  • Latent reservoir
  • Persistence
  • Provirus
  • Transcription

ASJC Scopus subject areas

  • Infectious Diseases
  • Virology

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