# Cytor lncRNA as a positive regulator of HIV gene expression and viral latency

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2022 · $179,800

## Abstract

ABSTRACT
To successfully eliminate the HIV reservoir, it is critical to understand the molecular events that control HIV
latency. While the key roles that host protein factors play in the regulation of HIV transcription and viral latency
have been extensively studied, our understanding of how the non-coding transcriptome, especially long non-
coding RNA (lncRNA), contribute to viral latency control is limited. To better understand the regulatory roles
lncRNAs play in the control of HIV transcription and viral latency, we employed RNA-Seq analysis and compared
the transcriptome in activated versus resting HIV-infected cells. We identified numerous lncRNAs that are
differentially expressed, therefore are candidates for HIV latency regulation. Among them, one lncRNA,
Cytoskeleton Regulator (Cytor), activates HIV transcription and viral latency. Our results also indicate that the
depletion of Cytor suppresses latent HIV reactivation by reducing the occupancy of RNA Polymerase II (Pol II)
and the levels of histone activation markers on the viral promoter. Additional biochemical and proteomic analyses
showed that Cytor occupies the HIV promoter and associates with Positive Transcription Elongation Factor b (P-
TEFb), which is an essential cellular factor for transcription elongation of HIV and cellular genes. In light of these
findings, we hypothesize that by recruiting P-TEFb to the HIV promoter, Cytor activates HIV gene expression.
To test this hypothesis, we will determine whether Cytor directly binds P-TEFb and recruits the cellular
transcription elongation complex to the HIV promoter. Additional preliminary RNA-Seq analysis indicated that
Cytor depletion results in broad changes in the host transcriptome. We will therefore identify downstream targets
of Cytor and determine their indirect effects on HIV gene expression. Significantly, our results will be further
confirmed in a clinically relevant context, as we will manipulate Cytor expression in CD4+ primary cells and
determine the magnitude of Cytor’s therapeutic potential for HIV reactivation and latency reversal or, alternatively,
to latency induction. Our study will provide new insights into the regulation of HIV transcription and viral latency
by lncRNAs. Its successful completion will lay the groundwork for the development of new RNA-based therapies
that will be added to current therapeutic protocols to eliminate HIV infection and the persistent viral reservoir.

## Key facts

- **NIH application ID:** 10548654
- **Project number:** 1R21AI170195-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Koh Fujinaga
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $179,800
- **Award type:** 1
- **Project period:** 2022-08-10 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10548654

## Citation

> US National Institutes of Health, RePORTER application 10548654, Cytor lncRNA as a positive regulator of HIV gene expression and viral latency (1R21AI170195-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10548654. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*