# Breaking into HIV-1’s Epigenetic Vault: Cure Strategies to Eliminate the Viral Reservoir

## TL;DR

This paper reviews strategies to cure HIV-1 by targeting the virus's hidden reservoir through epigenetic manipulation and CRISPR-Cas technology.

## Contribution

The paper provides a comprehensive review of current HIV-1 cure strategies focusing on epigenetic regulation and CRISPR-Cas therapeutics.

## Key findings

- Shock and Kill and Block and Lock are two major strategies targeting HIV-1 latency through chromatin modulation.
- CRISPR-Cas therapeutics show potential but are influenced by the chromatin architecture of the provirus.
- Chemical agents used in these strategies have varying clinical outcomes based on their mechanisms of action.

## Abstract

Human immunodeficiency virus type 1 (HIV-1) is a retrovirus that integrates into the host cell’s DNA as a provirus. Transcription from the provirus is regulated in large part by cellular proteins and epigenetic factors. These may be repressive or permissive to productive infection. The host factors that regulate this balance are therefore attractive targets for HIV-1 therapeutics. Indeed, proviral chromatin is the focus of two of the current HIV-1 cure strategies. “Shock and Kill” uses latency reversal agents to open the provirus’s chromatin, promoting high levels of gene expression that induce the killing of infected cells. “Block and Lock” uses latency promoting agents to induce heterochromatin, blocking transcription and forcing HIV-1 into a state of deep latency. Here, the compounds investigated in both strategies are reviewed, including their chemical structures, mechanisms of action, and clinical results. Finally, the use of CRISPR-Cas therapeutics and the impact of chromatin architecture on its efficacy are discussed.