Advancements in single-cell techniques for examining the HIV reservoir: pathways to a cure

ABSTRACT Human immunodeficiency virus (HIV) is largely incurable, due to the presence of a viral reservoir, which primarily consists of resting CD4+ T cells and other long-lived cells like macrophages. These reservoir cells, which persist despite suppressive antiretroviral therapy (ART), are thought...

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Main Authors: Nokuzola Mbhele, Benjamin Chimukangara, Lynn Tyers, Frank Maldarelli, Andrew D. Redd
Format: Article
Language:English
Published: American Society for Microbiology 2025-07-01
Series:mBio
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Online Access:https://journals.asm.org/doi/10.1128/mbio.00655-25
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author Nokuzola Mbhele
Benjamin Chimukangara
Lynn Tyers
Frank Maldarelli
Andrew D. Redd
author_facet Nokuzola Mbhele
Benjamin Chimukangara
Lynn Tyers
Frank Maldarelli
Andrew D. Redd
author_sort Nokuzola Mbhele
collection DOAJ
description ABSTRACT Human immunodeficiency virus (HIV) is largely incurable, due to the presence of a viral reservoir, which primarily consists of resting CD4+ T cells and other long-lived cells like macrophages. These reservoir cells, which persist despite suppressive antiretroviral therapy (ART), are thought to be influenced by several key factors such as position and orientation of chromosomal proviral integration, proviral intactness, and antigen specificity. The host’s immune status and immune selection pressures also likely play a significant role. Recent data suggest that the HIV provirus integrates into specific chromosomal regions, such as centromeric areas with low RNA expression, allowing the virus to evade detection. To effectively disrupt HIV latency, enhance immune recognition, and eliminate reservoir cells, a precise understanding of these viral reservoirs at single-cell level will be crucial. Gaining insights into the unique characteristics of these reservoir cells, including data on integration sites and gene expression profiles, is essential for designing targeted interventions. This review highlights current single-cell approaches, including single-cell sequencing, chromatin accessibility assays, and multiomic techniques, as tools for uncovering the heterogeneity and resilience of HIV reservoirs. Taken together, these methods aim to reveal the complexities of the HIV reservoir and promote the development of novel therapeutic strategies.
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spelling doaj-art-dafb4c4dea9342cbbd32435f030d494f2025-08-20T02:40:18ZengAmerican Society for MicrobiologymBio2150-75112025-07-0116710.1128/mbio.00655-25Advancements in single-cell techniques for examining the HIV reservoir: pathways to a cureNokuzola Mbhele0Benjamin Chimukangara1Lynn Tyers2Frank Maldarelli3Andrew D. Redd4Division of Medical Virology, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South AfricaCritical Care Medicine Department, NIH Clinical Center, Bethesda, Maryland, USADivision of Medical Virology, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South AfricaHIV Dynamics and Replication Program, National Cancer Institute, National Institutes of Health Bethesda, Bethesda, Maryland, USADivision of Medical Virology, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South AfricaABSTRACT Human immunodeficiency virus (HIV) is largely incurable, due to the presence of a viral reservoir, which primarily consists of resting CD4+ T cells and other long-lived cells like macrophages. These reservoir cells, which persist despite suppressive antiretroviral therapy (ART), are thought to be influenced by several key factors such as position and orientation of chromosomal proviral integration, proviral intactness, and antigen specificity. The host’s immune status and immune selection pressures also likely play a significant role. Recent data suggest that the HIV provirus integrates into specific chromosomal regions, such as centromeric areas with low RNA expression, allowing the virus to evade detection. To effectively disrupt HIV latency, enhance immune recognition, and eliminate reservoir cells, a precise understanding of these viral reservoirs at single-cell level will be crucial. Gaining insights into the unique characteristics of these reservoir cells, including data on integration sites and gene expression profiles, is essential for designing targeted interventions. This review highlights current single-cell approaches, including single-cell sequencing, chromatin accessibility assays, and multiomic techniques, as tools for uncovering the heterogeneity and resilience of HIV reservoirs. Taken together, these methods aim to reveal the complexities of the HIV reservoir and promote the development of novel therapeutic strategies.https://journals.asm.org/doi/10.1128/mbio.00655-25HIV-1HIV-1 reservoirsingle-cellHIV cure
spellingShingle Nokuzola Mbhele
Benjamin Chimukangara
Lynn Tyers
Frank Maldarelli
Andrew D. Redd
Advancements in single-cell techniques for examining the HIV reservoir: pathways to a cure
mBio
HIV-1
HIV-1 reservoir
single-cell
HIV cure
title Advancements in single-cell techniques for examining the HIV reservoir: pathways to a cure
title_full Advancements in single-cell techniques for examining the HIV reservoir: pathways to a cure
title_fullStr Advancements in single-cell techniques for examining the HIV reservoir: pathways to a cure
title_full_unstemmed Advancements in single-cell techniques for examining the HIV reservoir: pathways to a cure
title_short Advancements in single-cell techniques for examining the HIV reservoir: pathways to a cure
title_sort advancements in single cell techniques for examining the hiv reservoir pathways to a cure
topic HIV-1
HIV-1 reservoir
single-cell
HIV cure
url https://journals.asm.org/doi/10.1128/mbio.00655-25
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