# Regulation of Cell Death in HIV Reservoirs

> **NIH NIH R01** · METHODIST HOSPITAL RESEARCH INSTITUTE · 2024 · $593,795

## Abstract

ABSTRACT:
The combinational antiretroviral therapy is effective in suppressing HIV-1 replication. However,
latent HIV reservoirs cannot be cleared by such antiretroviral therapy, as viral rebound develops
rapidly after the treatment is interrupted in people living with HIV. The shock-and-kill approach to
eliminate HIV-1 reservoirs is to induce viral reactivation using latency reversal agents and trigger
cell death through virus-mediated cytopathic effects or immune-mediated clearance. However,
shock-and-kill by latency reversal agents has not been shown to successfully reduce the viral
reservoirs in HIV-1 patients. It has been reported that latency reversal agents can up-regulate
pro-survival autophagy and anti-apoptotic molecules that counteract cell death signaling.
Inhibition of these pro-survival mechanisms can promote the killing of HIV-1-infected cells, and
facilitate the killing of HIV-1 reservoir cells during vial re-activation. Experiments are proposed to
test hypothesis that cellular mechanisms that maintain the long-term persistence of HIV-1
reservoirs are important for protecting the reservoir cells against cell death, and targeting these
cellular mechanisms can sensitize HIV-1 reservoirs to cell death during viral reactivation: 1) To
determine the mechanisms for the specific induction of cell death in HIV-1 reservoirs in response
to viral reactivation. The mechanisms for the induction of apoptosis and alternative cell death
pathways in latent HIV-infected T cells by latency reversal agents will be tested; 2) To delineate
the mechanisms that confer the resistance to cell death in HIV-1 reservoirs upon viral reactivation;
and 3) To test whether targeting pro-survival mechanisms sensitizes HIV-1 reservoirs cells to cell
death during viral re-activation. The studies will reveal novel molecular pathways that could be
targeted to sensitize HIV-1 reservoirs to cell death, and facilitate the development of an effective
approach to clear HIV-1 reservoirs.

## Key facts

- **NIH application ID:** 10798296
- **Project number:** 5R01AI176558-02
- **Recipient organization:** METHODIST HOSPITAL RESEARCH INSTITUTE
- **Principal Investigator:** JIN WANG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $593,795
- **Award type:** 5
- **Project period:** 2023-03-01 → 2028-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10798296

## Citation

> US National Institutes of Health, RePORTER application 10798296, Regulation of Cell Death in HIV Reservoirs (5R01AI176558-02). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10798296. Licensed CC0.

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