Microglia Exhibit a Unique Intact HIV Reservoir in Human Postmortem Brain Tissue
A proviral reservoir persists within the central nervous system (CNS) of people with HIV, but its characteristics remain poorly understood. Research has primarily focused on cerebrospinal fluid (CSF), as acquiring brain tissue is challenging. We examined size, cellular tropism, and infection-dynamic...
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MDPI AG
2025-03-01
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| Online Access: | https://www.mdpi.com/1999-4915/17/4/467 |
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| author | Marieke M. Nühn Stephanie B. H. Gumbs Pauline J. Schipper Irene Drosou Lavina Gharu Ninée V. E. J. Buchholtz Gijsje J. L. J. Snijders Frederieke A. J. Gigase Annemarie M. J. Wensing Jori Symons Lot D. de Witte Monique Nijhuis |
| author_facet | Marieke M. Nühn Stephanie B. H. Gumbs Pauline J. Schipper Irene Drosou Lavina Gharu Ninée V. E. J. Buchholtz Gijsje J. L. J. Snijders Frederieke A. J. Gigase Annemarie M. J. Wensing Jori Symons Lot D. de Witte Monique Nijhuis |
| author_sort | Marieke M. Nühn |
| collection | DOAJ |
| description | A proviral reservoir persists within the central nervous system (CNS) of people with HIV, but its characteristics remain poorly understood. Research has primarily focused on cerebrospinal fluid (CSF), as acquiring brain tissue is challenging. We examined size, cellular tropism, and infection-dynamics of the viral reservoir in post-mortem brain tissue from five individuals on and off antiretroviral therapy (ART) across three brain regions. Microglia-enriched fractions (CD11b<sup>+</sup>) were isolated and levels of intact proviral DNA were quantified (IPDA). Full-length envelope reporter viruses were generated and characterized in CD4<sup>+</sup> T cells and monocyte-derived microglia. HIV DNA was observed in microglia-enriched fractions of all individuals, but intact proviruses were identified only in one ART-treated individual, representing 15% of the total proviruses. Phenotypic analyses of clones from this individual showed that 80% replicated efficiently in microglia and CD4<sup>+</sup> T cells, while the remaining viruses replicated only in CD4<sup>+</sup> T cells. No region-specific effects were observed. These results indicate a distinct HIV brain reservoir in microglia for all individuals, although intact proviruses were detected in only one. Given the unique immune environment of the CNS, the characteristics of microglia, and the challenges associated with targeting these cells, the CNS reservoir should be considered in cure strategies. |
| format | Article |
| id | doaj-art-c3387b545b2e4ced8fe474a5a92143f1 |
| institution | DOAJ |
| issn | 1999-4915 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj-art-c3387b545b2e4ced8fe474a5a92143f12025-08-20T03:13:33ZengMDPI AGViruses1999-49152025-03-0117446710.3390/v17040467Microglia Exhibit a Unique Intact HIV Reservoir in Human Postmortem Brain TissueMarieke M. Nühn0Stephanie B. H. Gumbs1Pauline J. Schipper2Irene Drosou3Lavina Gharu4Ninée V. E. J. Buchholtz5Gijsje J. L. J. Snijders6Frederieke A. J. Gigase7Annemarie M. J. Wensing8Jori Symons9Lot D. de Witte10Monique Nijhuis11Translational Virology, Department of Medical Microbiology, University Medical Center Utrecht, 3584 CX Utrecht, The NetherlandsTranslational Virology, Department of Medical Microbiology, University Medical Center Utrecht, 3584 CX Utrecht, The NetherlandsTranslational Virology, Department of Medical Microbiology, University Medical Center Utrecht, 3584 CX Utrecht, The NetherlandsTranslational Virology, Department of Medical Microbiology, University Medical Center Utrecht, 3584 CX Utrecht, The NetherlandsTranslational Virology, Department of Medical Microbiology, University Medical Center Utrecht, 3584 CX Utrecht, The NetherlandsTranslational Virology, Department of Medical Microbiology, University Medical Center Utrecht, 3584 CX Utrecht, The NetherlandsDepartment of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USADepartment of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USATranslational Virology, Department of Global Health and Bioethics, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, 3584 CX Utrecht, The NetherlandsTranslational Virology, Department of Medical Microbiology, University Medical Center Utrecht, 3584 CX Utrecht, The NetherlandsDepartment of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USATranslational Virology, Department of Medical Microbiology, University Medical Center Utrecht, 3584 CX Utrecht, The NetherlandsA proviral reservoir persists within the central nervous system (CNS) of people with HIV, but its characteristics remain poorly understood. Research has primarily focused on cerebrospinal fluid (CSF), as acquiring brain tissue is challenging. We examined size, cellular tropism, and infection-dynamics of the viral reservoir in post-mortem brain tissue from five individuals on and off antiretroviral therapy (ART) across three brain regions. Microglia-enriched fractions (CD11b<sup>+</sup>) were isolated and levels of intact proviral DNA were quantified (IPDA). Full-length envelope reporter viruses were generated and characterized in CD4<sup>+</sup> T cells and monocyte-derived microglia. HIV DNA was observed in microglia-enriched fractions of all individuals, but intact proviruses were identified only in one ART-treated individual, representing 15% of the total proviruses. Phenotypic analyses of clones from this individual showed that 80% replicated efficiently in microglia and CD4<sup>+</sup> T cells, while the remaining viruses replicated only in CD4<sup>+</sup> T cells. No region-specific effects were observed. These results indicate a distinct HIV brain reservoir in microglia for all individuals, although intact proviruses were detected in only one. Given the unique immune environment of the CNS, the characteristics of microglia, and the challenges associated with targeting these cells, the CNS reservoir should be considered in cure strategies.https://www.mdpi.com/1999-4915/17/4/467HIVbrainCNSreplication-competentcellular tropismmicroglia |
| spellingShingle | Marieke M. Nühn Stephanie B. H. Gumbs Pauline J. Schipper Irene Drosou Lavina Gharu Ninée V. E. J. Buchholtz Gijsje J. L. J. Snijders Frederieke A. J. Gigase Annemarie M. J. Wensing Jori Symons Lot D. de Witte Monique Nijhuis Microglia Exhibit a Unique Intact HIV Reservoir in Human Postmortem Brain Tissue Viruses HIV brain CNS replication-competent cellular tropism microglia |
| title | Microglia Exhibit a Unique Intact HIV Reservoir in Human Postmortem Brain Tissue |
| title_full | Microglia Exhibit a Unique Intact HIV Reservoir in Human Postmortem Brain Tissue |
| title_fullStr | Microglia Exhibit a Unique Intact HIV Reservoir in Human Postmortem Brain Tissue |
| title_full_unstemmed | Microglia Exhibit a Unique Intact HIV Reservoir in Human Postmortem Brain Tissue |
| title_short | Microglia Exhibit a Unique Intact HIV Reservoir in Human Postmortem Brain Tissue |
| title_sort | microglia exhibit a unique intact hiv reservoir in human postmortem brain tissue |
| topic | HIV brain CNS replication-competent cellular tropism microglia |
| url | https://www.mdpi.com/1999-4915/17/4/467 |
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