Single-cell analyses identify monocyte gene expression profiles that influence HIV-1 reservoir size in acutely treated cohorts
Abstract Eliminating latent HIV-1 is a major goal of AIDS research but host factors determining the size of these reservoirs are poorly understood. Here, we investigate the role of host gene expression on HIV-1 reservoir size during suppressive antiretroviral therapy (ART). Peripheral blood cells of...
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2025-05-01
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| Online Access: | https://doi.org/10.1038/s41467-025-59833-9 |
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| author | Philip K. Ehrenberg Aviva Geretz Meta Volcic Taisuke Izumi Lauren K. Yum Adam Waickman Shida Shangguan Dominic Paquin-Proulx Matthew Creegan Meera Bose Kawthar Machmach Aidan McGraw Akshara Narahari Jeffrey R. Currier Carlo Sacdalan Nittaya Phanuphak Richard Apps Michael Corley Lishomwa C. Ndhlovu Bonnie Slike Shelly J. Krebs Jintanat Anonworanich Sodsai Tovanabutra Merlin L. Robb Michael A. Eller Gregory M. Laird Joshua Cyktor Eric S. Daar Trevor A. Crowell John W. Mellors Sandhya Vasan Nelson L. Michael Frank Kirchhoff Rasmi Thomas |
| author_facet | Philip K. Ehrenberg Aviva Geretz Meta Volcic Taisuke Izumi Lauren K. Yum Adam Waickman Shida Shangguan Dominic Paquin-Proulx Matthew Creegan Meera Bose Kawthar Machmach Aidan McGraw Akshara Narahari Jeffrey R. Currier Carlo Sacdalan Nittaya Phanuphak Richard Apps Michael Corley Lishomwa C. Ndhlovu Bonnie Slike Shelly J. Krebs Jintanat Anonworanich Sodsai Tovanabutra Merlin L. Robb Michael A. Eller Gregory M. Laird Joshua Cyktor Eric S. Daar Trevor A. Crowell John W. Mellors Sandhya Vasan Nelson L. Michael Frank Kirchhoff Rasmi Thomas |
| author_sort | Philip K. Ehrenberg |
| collection | DOAJ |
| description | Abstract Eliminating latent HIV-1 is a major goal of AIDS research but host factors determining the size of these reservoirs are poorly understood. Here, we investigate the role of host gene expression on HIV-1 reservoir size during suppressive antiretroviral therapy (ART). Peripheral blood cells of fourteen males initiating ART during acute infection and demonstrating effective viral suppression but varying magnitudes of total HIV-1 DNA were characterized by single-cell RNA sequencing. Differential expression analysis demonstrates increased CD14+ monocyte activity in participants having undetectable HIV-1 reservoirs, with IL1B expression inversely associating with reservoir size. This is validated in another cohort of 38 males comprised of different ancestry and HIV-1 subtypes, and with intact proviral DNA assay (IPDA®) measurements. Modeling interactions show monocyte IL1B expression associates inversely with reservoir size at higher frequencies of central memory CD4+ T cells, linking monocyte IL1B expression to cell types known to be reservoirs for persistent HIV-1. Functional analyses reveal that IL1B activates NF-κB, thereby promoting productive HIV-1 infection while simultaneously suppressing viral spread, suggesting a natural latency reversing activity to deplete the reservoir in ART-treated individuals. Altogether, scRNA-seq analyses reveal that monocyte IL1B expression could decrease HIV-1 proviral reservoirs in individuals initiating ART during acute infection. |
| format | Article |
| id | doaj-art-0ca7c11fb93b417fb3f006a7f29ed73b |
| institution | OA Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
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| spelling | doaj-art-0ca7c11fb93b417fb3f006a7f29ed73b2025-08-20T02:03:36ZengNature PortfolioNature Communications2041-17232025-05-0116111610.1038/s41467-025-59833-9Single-cell analyses identify monocyte gene expression profiles that influence HIV-1 reservoir size in acutely treated cohortsPhilip K. Ehrenberg0Aviva Geretz1Meta Volcic2Taisuke Izumi3Lauren K. Yum4Adam Waickman5Shida Shangguan6Dominic Paquin-Proulx7Matthew Creegan8Meera Bose9Kawthar Machmach10Aidan McGraw11Akshara Narahari12Jeffrey R. Currier13Carlo Sacdalan14Nittaya Phanuphak15Richard Apps16Michael Corley17Lishomwa C. Ndhlovu18Bonnie Slike19Shelly J. Krebs20Jintanat Anonworanich21Sodsai Tovanabutra22Merlin L. Robb23Michael A. Eller24Gregory M. Laird25Joshua Cyktor26Eric S. Daar27Trevor A. Crowell28John W. Mellors29Sandhya Vasan30Nelson L. Michael31Frank Kirchhoff32Rasmi Thomas33U.S. Military HIV Research Program, Center for Infectious Disease Research, Walter Reed Army Institute of ResearchU.S. Military HIV Research Program, Center for Infectious Disease Research, Walter Reed Army Institute of ResearchInstitute of Molecular Virology, Ulm University Medical CenterU.S. Military HIV Research Program, Center for Infectious Disease Research, Walter Reed Army Institute of ResearchU.S. Military HIV Research Program, Center for Infectious Disease Research, Walter Reed Army Institute of ResearchViral Diseases Program, Walter Reed Army Institute of ResearchU.S. Military HIV Research Program, Center for Infectious Disease Research, Walter Reed Army Institute of ResearchU.S. Military HIV Research Program, Center for Infectious Disease Research, Walter Reed Army Institute of ResearchU.S. Military HIV Research Program, Center for Infectious Disease Research, Walter Reed Army Institute of ResearchU.S. Military HIV Research Program, Center for Infectious Disease Research, Walter Reed Army Institute of ResearchU.S. Military HIV Research Program, Center for Infectious Disease Research, Walter Reed Army Institute of ResearchDepartment of Biology, College of Arts and Sciences, American UniversityDepartment of Biology, College of Arts and Sciences, Saint Joseph’s UniversityViral Diseases Program, Walter Reed Army Institute of ResearchSEARCH Research FoundationInstitute of HIV Research and InnovationNIH Center for Human Immunology, National Institutes of HealthDepartment of Medicine, Division of Infectious Diseases, Weill Cornell MedicineDepartment of Medicine, Division of Infectious Diseases, Weill Cornell MedicineU.S. Military HIV Research Program, Center for Infectious Disease Research, Walter Reed Army Institute of ResearchU.S. Military HIV Research Program, Center for Infectious Disease Research, Walter Reed Army Institute of ResearchU.S. Military HIV Research Program, Center for Infectious Disease Research, Walter Reed Army Institute of ResearchU.S. Military HIV Research Program, Center for Infectious Disease Research, Walter Reed Army Institute of ResearchU.S. Military HIV Research Program, Center for Infectious Disease Research, Walter Reed Army Institute of ResearchU.S. Military HIV Research Program, Center for Infectious Disease Research, Walter Reed Army Institute of ResearchAccelevir DiagnosticsDepartment of Medicine, University of PittsburghLundquist Institute at Harbor-UCLA Medical CenterU.S. Military HIV Research Program, Center for Infectious Disease Research, Walter Reed Army Institute of ResearchDepartment of Medicine, University of PittsburghU.S. Military HIV Research Program, Center for Infectious Disease Research, Walter Reed Army Institute of ResearchCenter for Infectious Disease Research, Walter Reed Army Institute of ResearchInstitute of Molecular Virology, Ulm University Medical CenterU.S. Military HIV Research Program, Center for Infectious Disease Research, Walter Reed Army Institute of ResearchAbstract Eliminating latent HIV-1 is a major goal of AIDS research but host factors determining the size of these reservoirs are poorly understood. Here, we investigate the role of host gene expression on HIV-1 reservoir size during suppressive antiretroviral therapy (ART). Peripheral blood cells of fourteen males initiating ART during acute infection and demonstrating effective viral suppression but varying magnitudes of total HIV-1 DNA were characterized by single-cell RNA sequencing. Differential expression analysis demonstrates increased CD14+ monocyte activity in participants having undetectable HIV-1 reservoirs, with IL1B expression inversely associating with reservoir size. This is validated in another cohort of 38 males comprised of different ancestry and HIV-1 subtypes, and with intact proviral DNA assay (IPDA®) measurements. Modeling interactions show monocyte IL1B expression associates inversely with reservoir size at higher frequencies of central memory CD4+ T cells, linking monocyte IL1B expression to cell types known to be reservoirs for persistent HIV-1. Functional analyses reveal that IL1B activates NF-κB, thereby promoting productive HIV-1 infection while simultaneously suppressing viral spread, suggesting a natural latency reversing activity to deplete the reservoir in ART-treated individuals. Altogether, scRNA-seq analyses reveal that monocyte IL1B expression could decrease HIV-1 proviral reservoirs in individuals initiating ART during acute infection.https://doi.org/10.1038/s41467-025-59833-9 |
| spellingShingle | Philip K. Ehrenberg Aviva Geretz Meta Volcic Taisuke Izumi Lauren K. Yum Adam Waickman Shida Shangguan Dominic Paquin-Proulx Matthew Creegan Meera Bose Kawthar Machmach Aidan McGraw Akshara Narahari Jeffrey R. Currier Carlo Sacdalan Nittaya Phanuphak Richard Apps Michael Corley Lishomwa C. Ndhlovu Bonnie Slike Shelly J. Krebs Jintanat Anonworanich Sodsai Tovanabutra Merlin L. Robb Michael A. Eller Gregory M. Laird Joshua Cyktor Eric S. Daar Trevor A. Crowell John W. Mellors Sandhya Vasan Nelson L. Michael Frank Kirchhoff Rasmi Thomas Single-cell analyses identify monocyte gene expression profiles that influence HIV-1 reservoir size in acutely treated cohorts Nature Communications |
| title | Single-cell analyses identify monocyte gene expression profiles that influence HIV-1 reservoir size in acutely treated cohorts |
| title_full | Single-cell analyses identify monocyte gene expression profiles that influence HIV-1 reservoir size in acutely treated cohorts |
| title_fullStr | Single-cell analyses identify monocyte gene expression profiles that influence HIV-1 reservoir size in acutely treated cohorts |
| title_full_unstemmed | Single-cell analyses identify monocyte gene expression profiles that influence HIV-1 reservoir size in acutely treated cohorts |
| title_short | Single-cell analyses identify monocyte gene expression profiles that influence HIV-1 reservoir size in acutely treated cohorts |
| title_sort | single cell analyses identify monocyte gene expression profiles that influence hiv 1 reservoir size in acutely treated cohorts |
| url | https://doi.org/10.1038/s41467-025-59833-9 |
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