Neuroinflammation associated with proviral DNA persists in the brain of virally suppressed people with HIV
Despite viral suppression with antiretroviral therapy (ART), people with HIV (PWH) continue to exhibit brain pathology, and ~20% of individuals develop HIV-associated neurocognitive disorders. However, the state of cellular activation in the brain of virally suppressed (VS) PWH and the impact of loc...
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Frontiers Media S.A.
2025-05-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1570692/full |
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| author | Sarah J. Byrnes Janna Jamal Eddine Jingling Zhou Emily Chalmers Emma Wanicek Narin Osman Trisha A. Jenkins Michael Roche Michael Roche Bruce J. Brew Bruce J. Brew Jacob D. Estes Jacob D. Estes Thomas A. Angelovich Thomas A. Angelovich Thomas A. Angelovich Melissa J. Churchill Melissa J. Churchill Melissa J. Churchill |
| author_facet | Sarah J. Byrnes Janna Jamal Eddine Jingling Zhou Emily Chalmers Emma Wanicek Narin Osman Trisha A. Jenkins Michael Roche Michael Roche Bruce J. Brew Bruce J. Brew Jacob D. Estes Jacob D. Estes Thomas A. Angelovich Thomas A. Angelovich Thomas A. Angelovich Melissa J. Churchill Melissa J. Churchill Melissa J. Churchill |
| author_sort | Sarah J. Byrnes |
| collection | DOAJ |
| description | Despite viral suppression with antiretroviral therapy (ART), people with HIV (PWH) continue to exhibit brain pathology, and ~20% of individuals develop HIV-associated neurocognitive disorders. However, the state of cellular activation in the brain of virally suppressed (VS) PWH and the impact of local viral reservoirs on cellular activation are unclear. Using multiplex immunofluorescence imaging, here, we demonstrate that the frontal cortex brain tissue from both non-virally suppressed (nVS; n=17) and VS PWH (n=18) have higher frequencies of astrocytes and myeloid cells expressing interferon-inducible Mx-1 and proinflammatory TNFα relative to HIV-seronegative individuals (p<0.05 for all). The frequency of TGF-β1+ cells were also elevated in the brain tissue from both nVS and VS PWH, which may support active immunoregulatory responses despite ART. Importantly, the frequency of Mx1+ myeloid cells correlated with levels of total HIV DNA and intact and 5′ defective HIV proviral DNA (p<0.05 for all) in the brain of VS PWH. These findings demonstrate that cell activation persists in the brain of VS PWH and is associated with HIV DNA in the brain, which may contribute to neuropathology. |
| format | Article |
| id | doaj-art-1817e83e3bc6475a96aa0c10ca5ac8b1 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-1817e83e3bc6475a96aa0c10ca5ac8b12025-08-20T03:47:28ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-05-011610.3389/fimmu.2025.15706921570692Neuroinflammation associated with proviral DNA persists in the brain of virally suppressed people with HIVSarah J. Byrnes0Janna Jamal Eddine1Jingling Zhou2Emily Chalmers3Emma Wanicek4Narin Osman5Trisha A. Jenkins6Michael Roche7Michael Roche8Bruce J. Brew9Bruce J. Brew10Jacob D. Estes11Jacob D. Estes12Thomas A. Angelovich13Thomas A. Angelovich14Thomas A. Angelovich15Melissa J. Churchill16Melissa J. Churchill17Melissa J. Churchill18ATRACT Research Centre, School of Health and Biomedical Sciences, RMIT University, Melbourne, VIC, AustraliaATRACT Research Centre, School of Health and Biomedical Sciences, RMIT University, Melbourne, VIC, AustraliaATRACT Research Centre, School of Health and Biomedical Sciences, RMIT University, Melbourne, VIC, AustraliaATRACT Research Centre, School of Health and Biomedical Sciences, RMIT University, Melbourne, VIC, AustraliaATRACT Research Centre, School of Health and Biomedical Sciences, RMIT University, Melbourne, VIC, AustraliaATRACT Research Centre, School of Health and Biomedical Sciences, RMIT University, Melbourne, VIC, AustraliaATRACT Research Centre, School of Health and Biomedical Sciences, RMIT University, Melbourne, VIC, AustraliaATRACT Research Centre, School of Health and Biomedical Sciences, RMIT University, Melbourne, VIC, AustraliaDepartment of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, AustraliaDepartment of Neurology and Immunology, Peter Duncan Neuroscience Unit, St Vincent’s Hospital, University of New South Wales, Darlinghurst, NSW, AustraliaUniversity of Notre Dame, Sydney, NSW, AustraliaATRACT Research Centre, School of Health and Biomedical Sciences, RMIT University, Melbourne, VIC, AustraliaVaccine & Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR, United StatesATRACT Research Centre, School of Health and Biomedical Sciences, RMIT University, Melbourne, VIC, AustraliaDepartment of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, AustraliaLife Sciences, Burnet Institute, Melbourne, VIC, AustraliaATRACT Research Centre, School of Health and Biomedical Sciences, RMIT University, Melbourne, VIC, AustraliaDepartment of Microbiology, Monash University, Melbourne, VIC, AustraliaDepartment of Medicine, Monash University, Melbourne, VIC, AustraliaDespite viral suppression with antiretroviral therapy (ART), people with HIV (PWH) continue to exhibit brain pathology, and ~20% of individuals develop HIV-associated neurocognitive disorders. However, the state of cellular activation in the brain of virally suppressed (VS) PWH and the impact of local viral reservoirs on cellular activation are unclear. Using multiplex immunofluorescence imaging, here, we demonstrate that the frontal cortex brain tissue from both non-virally suppressed (nVS; n=17) and VS PWH (n=18) have higher frequencies of astrocytes and myeloid cells expressing interferon-inducible Mx-1 and proinflammatory TNFα relative to HIV-seronegative individuals (p<0.05 for all). The frequency of TGF-β1+ cells were also elevated in the brain tissue from both nVS and VS PWH, which may support active immunoregulatory responses despite ART. Importantly, the frequency of Mx1+ myeloid cells correlated with levels of total HIV DNA and intact and 5′ defective HIV proviral DNA (p<0.05 for all) in the brain of VS PWH. These findings demonstrate that cell activation persists in the brain of VS PWH and is associated with HIV DNA in the brain, which may contribute to neuropathology.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1570692/fullHIVbrainneuroinflammationreservoirsmicrogliaastrocytes |
| spellingShingle | Sarah J. Byrnes Janna Jamal Eddine Jingling Zhou Emily Chalmers Emma Wanicek Narin Osman Trisha A. Jenkins Michael Roche Michael Roche Bruce J. Brew Bruce J. Brew Jacob D. Estes Jacob D. Estes Thomas A. Angelovich Thomas A. Angelovich Thomas A. Angelovich Melissa J. Churchill Melissa J. Churchill Melissa J. Churchill Neuroinflammation associated with proviral DNA persists in the brain of virally suppressed people with HIV Frontiers in Immunology HIV brain neuroinflammation reservoirs microglia astrocytes |
| title | Neuroinflammation associated with proviral DNA persists in the brain of virally suppressed people with HIV |
| title_full | Neuroinflammation associated with proviral DNA persists in the brain of virally suppressed people with HIV |
| title_fullStr | Neuroinflammation associated with proviral DNA persists in the brain of virally suppressed people with HIV |
| title_full_unstemmed | Neuroinflammation associated with proviral DNA persists in the brain of virally suppressed people with HIV |
| title_short | Neuroinflammation associated with proviral DNA persists in the brain of virally suppressed people with HIV |
| title_sort | neuroinflammation associated with proviral dna persists in the brain of virally suppressed people with hiv |
| topic | HIV brain neuroinflammation reservoirs microglia astrocytes |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1570692/full |
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