# BCA2's modulation of NF-kB and its role in proviral latency

> **NIH NIH R21** · TEXAS TECH UNIVERSITY · 2020 · $30,708

## Abstract

PROJECT SUMMARY
 BCA2 (Breast Cancer-Associated gene 2, also known as RNF115, ZNF364 or Rabring7) is a RING-finger
E3 ubiquitin ligase with anti-HIV activity. In particular, BCA2 promotes the lysosomal degradation of Gag,
thereby inhibiting virion assembly (Nityanandam and Serra-Moreno, 2014). We now have evidence that BCA2
provides a regulatory negative feedback on NF-κB (Colomer-Lluch and Serra-Moreno, 2017), a pro-
inflammatory cascade elicited upon infection. Remarkably, HIV-1 takes advantage of this innate cascade to
ensure gene expression and genome replication by enhancing viral transcription. However, the inactivation of
NF-κB is a major determinant towards the establishment of a latent infection. Currently, the latent reservoir, a
group of long-lived cells carrying latent HIV-1 proviruses, represents the most critical barrier to functionally cure
HIV/AIDS. Since BCA2 blocks NF-κB, we predict that this activity enforces proviral latency. We will test this
hypothesis by (1) elucidating the molecular mechanism by which BCA2 modulates NF-κB, and its effects on
the transcriptional capacity of HIV-1, and (2) assessing the implication of BCA2 in the establishment and
maintenance of proviral latency. These studies will increase our fundamental understanding of the
mechanisms involved in the establishment of proviral latency, with the ultimate goal of exploiting them to
permanently disable the latent reservoir.

## Key facts

- **NIH application ID:** 9828615
- **Project number:** 5R21AI138589-02
- **Recipient organization:** TEXAS TECH UNIVERSITY
- **Principal Investigator:** Ruth Serra Moreno
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $30,708
- **Award type:** 5
- **Project period:** 2018-11-23 → 2020-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9828615

## Citation

> US National Institutes of Health, RePORTER application 9828615, BCA2's modulation of NF-kB and its role in proviral latency (5R21AI138589-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9828615. Licensed CC0.

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