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Targeting HIV myeloid and central nervous system reservoirs for HIV cure
Paula Grasberger1, Kiera L Clayton
1Department of Pathology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Purpose Of Review:
Myeloid vs. CD4 + T-cell reservoirs have received less attention for HIV cure strategies, mainly due to more limited access to tissues andchallenging in vitro and in vivo models, including modeling how myeloid cells affect HIV-associated neurocognitive disorder (HAND). This review highlights recent studies providing insights intomyeloid viral reservoirs, new methods to study them, and the strategies to target them.
Recent Findings:
In addition to studies describing replication competent virus derived from blood monocytes, which correlates with HAND, myeloid-derived virus can be characterized in clinical samples, such as the blood, using virion immunocapture. Characterization of monocyte subsets and pro-inflammatory markers in the blood can also help detect HAND. New humanized mouse models and in vitro organoid models have improved our ability to study central nervous system (CNS) reservoirs and inflammation. Strategies targeting the CNS vs. peripheral reservoirs may need to be fundamentally different to limit inflammation and which may contribute toHAND.
Summary:
Insights provided by these recent studies should challenge the field to employ these methods for myeloid reservoir and HAND detection in preclinical and clinical trial studies. Future HIV cure proposals can aim to include a myeloid reservoir component to help guide the design of strategies for inclusive cure strategies.
Insights
Investigating myeloid cell reservoirs is crucial for developing effective HIV cure strategies. Recent advancements offer new methods to study these reservoirs and target them, potentially improving treatments for HIV-associated neurocognitive disorder (HAND).
Area of Science:
- Virology
- Immunology
- Neuroscience
Background:
- Myeloid cell reservoirs in HIV have been understudied compared to CD4+ T-cell reservoirs due to challenges in accessing tissues and developing suitable models.
- Understanding myeloid reservoirs is critical for developing comprehensive HIV cure strategies and addressing HIV-associated neurocognitive disorder (HAND).
- Existing models for studying myeloid cells and their role in HIV, particularly in the central nervous system (CNS), are limited.
Purpose of the Study:
- To review recent studies on myeloid viral reservoirs in HIV.
- To highlight novel methods for studying myeloid reservoirs.
- To discuss strategies for targeting myeloid reservoirs in HIV cure research, with a focus on HAND.
Main Methods:
- Review of recent scientific literature on myeloid reservoirs and HIV cure.
- Analysis of methods like virion immunocapture for characterizing myeloid-derived virus in clinical samples.
- Evaluation of new in vitro organoid and humanized mouse models for studying CNS reservoirs and inflammation.
Main Results:
- Replication-competent virus from blood monocytes correlates with HAND.
- Virion immunocapture and characterization of monocyte subsets/inflammatory markers aid in HAND detection.
- New models improve the study of CNS reservoirs and inflammation, suggesting different targeting strategies for CNS vs. peripheral reservoirs.
Conclusions:
- Recent insights necessitate the use of advanced methods for myeloid reservoir and HAND detection in preclinical and clinical studies.
- Future HIV cure strategies should incorporate myeloid reservoir components for more inclusive approaches.
- Targeting strategies for CNS and peripheral reservoirs may need to be distinct to mitigate inflammation contributing to HAND.
