Viruses, Vol. 15, Pages 1969: Transcriptional Stochasticity as a Key Aspect of HIV-1 Latency

Viruses, Vol. 15, Pages 1969: Transcriptional Stochasticity as a Key Aspect of HIV-1 Latency
Viruses doi: 10.3390/v15091969
Authors:
Alexia Damour
Vera Slaninova
Ovidiu Radulescu
Edouard Bertrand
Eugenia Basyuk

This review summarizes current advances in the role of transcriptional stochasticity in HIV-1 latency, which were possible in a large part due to the development of single-cell approaches. HIV-1 transcription proceeds in bursts of RNA production, which stem from the stochastic switching of the viral promoter between ON and OFF states. This switching is caused by random binding dynamics of transcription factors and nucleosomes to the viral promoter and occurs at several time scales from minutes to hours. Transcriptional bursts are mainly controlled by the core transcription factors TBP, SP1 and NF-κb, the chromatin status of the viral promoter and RNA polymerase II pausing. In particular, spontaneous variability in the promoter chromatin creates heterogeneity in the response to activators such as TNF-α, which is then amplified by the Tat feedback loop to generate high and low viral transcriptional states. This phenomenon is likely at the basis of the partial and stochastic response of latent T cells from HIV-1 patients to latency-reversing agents, which is a barrier for the development of shock-and-kill strategies of viral eradication. A detailed understanding of the transcriptional stochasticity of HIV-1 and the possibility t...

Source: Viruses - September 21, 2023 Category: Virology Authors: Alexia Damour Vera Slaninova Ovidiu Radulescu Edouard Bertrand Eugenia Basyuk Tags: Review Source Type: research