# Control of HIV-1 Transcription by CPSF6 and PP2A

> **NIH NIH R21** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2024 · $192,500

## Abstract

PROJECT SUMMARY
 The major barrier toward the eradication of HIV-1 infection is the presence of a small reservoir of latently
infected cells that escape immune-mediated clearance. Due to the lack of transcriptional activity, latent
proviruses in vivo are not easily detectable and cannot be targeted by either natural immune mechanisms or
molecular therapies. Therefore, understanding how HIV-1 transcription is regulated will open doors to novel
therapeutic strategies targeting the latent reservoir.
 Pharmacological approaches to reactivate the latent reservoir in vivo have been considered as potential
eradication therapies for more than a decade. However, the effectiveness of these approaches has been
disappointing as only a minority of latently infected cells appear to be responsive to latency-reversing agents. A
deeper understanding of the transcriptional regulation of the HIV-1 promoter is necessary before we can design
novel and effective LRAs. Cleavage and polyadenylation specificity factor 6 (CPSF6) is a cellular protein with
multiple functions both in cellular and viral biology. Our recent finding that CPSF6 controls the stability and activity
of PP2A, a phosphatase directly implicated in the de-phosphorylation and inactivation of CDK9 and RNA Pol II,
reveals an exciting new line of investigation into potential cure strategies. This proposal will focus on the following
innovative directions: (a) to further understand the factors regulating HIV-1 transcription, with a focus on CPSF6
and PP2A; (b) to explore the possibility of using PP2A inhibition as a method to reactivate latent viruses; and (3)
to further explore the unknown functions of CPSF6 based on a recent proteomics experiment from our group
yielding several exciting hits.

## Key facts

- **NIH application ID:** 10900777
- **Project number:** 5R21AI176884-02
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** VICENTE PLANELLES
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $192,500
- **Award type:** 5
- **Project period:** 2023-08-07 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10900777

## Citation

> US National Institutes of Health, RePORTER application 10900777, Control of HIV-1 Transcription by CPSF6 and PP2A (5R21AI176884-02). Retrieved via AI Analytics 2026-06-04 from https://api.ai-analytics.org/grant/nih/10900777. Licensed CC0.

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