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Updated: Mar 29, 2026
Phagosome Migration and Velocity Measured in Live Primary Human Macrophages Infected with HIV-1
Published on: September 5, 2016
To Kill a Macrophage: Targeted Strategies to Eliminate Macrophage Reservoirs of HIV
Laura Rikard-Bell1,2, Morgane Brunton-O'Sullivan1, Sushama Telwatte3
1Life Sciences Discipline, Burnet Institute, Melbourne, VIC 3004, Australia.
Abstract:
Persistent HIV reservoirs in long-lived macrophages pose a unique and formidable challenge to achieving HIV cure. HIV-infected macrophages are more resistant than CD4+ T cells to both virus- and immune-mediated death pathways including apoptosis, facilitating their persistence in tissue sanctuary sites and potential to contribute to viral rebound upon therapy cessation. This resistance is driven by HIV-induced modulation of both intrinsic and extrinsic apoptotic pathways, alongside survival mechanisms including autophagy. In this review, we examine the biological mechanisms promoting macrophage survival and explore novel translational strategies aimed at subverting this resistance. Crucially, we highlight the methodological limitations hindering progress, including the scarcity of robust in vitro macrophage models, the influence of culture conditions, and physiological relevance to macrophages in vivo. We emphasise that a macrophage-inclusive approach, incorporating improved pre-clinical models and developing clinical measurements to quantify the reservoir in human tissue, is essential to successfully eliminate this distinct reservoir and advance toward sustained ART-free remission.
Insights
Persistent HIV reservoirs in macrophages present a major hurdle to curing HIV. Understanding macrophage survival mechanisms and improving research models are key to eliminating this reservoir and achieving long-term remission.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Persistent human immunodeficiency virus (HIV) reservoirs in macrophages are a significant obstacle to HIV cure.
- Macrophages are more resistant to cell death pathways than CD4+ T cells, contributing to viral persistence in sanctuary sites.
Purpose of the Study:
- To review the biological mechanisms that promote macrophage survival during HIV infection.
- To explore novel translational strategies for overcoming macrophage-mediated HIV persistence.
- To highlight methodological limitations in current research models.
Main Methods:
- Review of existing literature on HIV reservoirs in macrophages.
- Analysis of cellular survival mechanisms, including apoptosis and autophagy.
- Discussion of pre-clinical models and potential clinical measurements.
Main Results:
- HIV infection modulates intrinsic and extrinsic apoptotic pathways in macrophages, enhancing their survival.
- Autophagy contributes to macrophage survival and HIV persistence.
- Current in vitro macrophage models have limitations in physiological relevance.
Conclusions:
- A macrophage-inclusive approach is essential for HIV cure strategies.
- Improved pre-clinical models and clinical measurements are needed to quantify macrophage reservoirs.
- Targeting macrophage survival mechanisms is crucial for sustained ART-free remission.
