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Updated: Nov 3, 2025

High Throughput In Vitro Assessment of Latency Reversing Agents on HIV Transcription and Splicing
Published on: January 22, 2019
Brain HIV-1 latently-infected reservoirs targeted by the suicide gene strategy
Sepideh Saeb1,2, Mehrdad Ravanshad3, Mahmoud Reza Pourkarim4
1Department of Virology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Abstract:
Reducing the pool of HIV-1 reservoirs in patients is a must to achieve functional cure. The most prominent HIV-1 cell reservoirs are resting CD4 + T cells and brain derived microglial cells. Infected microglial cells are believed to be the source of peripheral tissues reseedings and the emergence of drug resistance. Clearing infected cells from the brain is therefore crucial. However, many characteristics of microglial cells and the central nervous system make extremely difficult their eradication from brain reservoirs. Current methods, such as the "shock and kill", the "block and lock" and gene editing strategies cannot override these difficulties. Therefore, new strategies have to be designed when considering the elimination of brain reservoirs. We set up an original gene suicide strategy using latently infected microglial cells as model cells. In this paper we provide proof of concept of this strategy.
Insights
A novel gene suicide strategy shows promise for eliminating latent HIV-1 reservoirs in brain microglial cells, a critical step toward a functional cure for HIV.
Area of Science:
- Neuroscience
- Immunology
- Virology
Background:
- HIV-1 reservoirs, particularly in resting CD4+ T cells and brain microglial cells, impede functional cure.
- Infected microglial cells contribute to viral rebound and drug resistance.
- Eradicating HIV-1 from the central nervous system is challenging due to microglial cell properties and the brain environment.
Purpose of the Study:
- To develop and validate a novel gene suicide strategy for eliminating latent HIV-1 reservoirs in microglial cells.
- To address the limitations of current HIV-1 eradication methods in the brain.
Main Methods:
- Utilized latently HIV-1 infected microglial cells as a model system.
- Designed and implemented an original gene suicide strategy targeting these cells.
Main Results:
- Provided proof of concept for the efficacy of the proposed gene suicide strategy.
- Demonstrated the potential for eliminating infected microglial cells from brain reservoirs.
Conclusions:
- The developed gene suicide strategy offers a new approach for targeting and eliminating HIV-1 reservoirs in the brain.
- This strategy may overcome the challenges associated with current methods for HIV-1 eradication in the central nervous system.
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