Integrator complex subunit 12 knockout overcomes a transcriptional block to HIV latency reversal

The latent HIV reservoir is a major barrier to HIV cure. Combining latency reversal agents (LRAs) with differing mechanisms of action such as AZD5582, a non-canonical NF-kB activator, and I-BET151, a bromodomain inhibitor is appealing towards inducing HIV-1 reactivation. However, even this LRA combination needs improvement as it is inefficient at activating proviruses in cells from people living with HIV (PLWH). In this study, we performed a CRISPR screen in conjunction with AZD5582 & I-BET151 and identified a member of the Integrator complex as a target to improve this LRA combination, specifically Integrator complex subunit 12 (INTS12), as we see enrichment of this gene over all others. Integrator functions as a genome-wide attenuator of transcription that acts on elongation through its RNA cleavage and phosphatase modules. We observed knockout of INTS12 improved latency reactivation at the transcriptional level in J-lat cells compared to the safe-harbor locus AAVS1 knockout. INTS..., , # Integrator complex subunit 12 knockout overcomes a transcriptional block to HIV latency reversal

Dataset DOI: [10.5061/dryad.qfttdz0t0](10.5061/dryad.qfttdz0t0)

## Description of the data and file structure

This data was collected to assess the effects of INTS12 knockout on HIV latency reversal on its own and in the presence of AZD5582 & I-BET151.

### Files and variables

#### File: 250323\_DryadInformation.xlsx

**Description:** 

There are 14 tabs total in this Excel:

Tab 1 is a read me with general information, Tabs 2-8 correspond to each main figure from the manuscript, example: Figure1, Tabs 9-14 correspond to each supplementary figure from the manuscript, example: Figure1_Supp1 means Figure 1 supplementary figure 1. Each tab contains all data pertaining to a specific figure (for instance Figure 1 will include Figure 1B and 1C information, as those have graphical data) in the closest format to how the data was graphed. For this reason, some values may be included in a separ...,