Chronic immune activation and gut barrier dysfunction is associated with neuroinflammation in ART-suppressed SIV+ rhesus macaques.
HIV-associated neurocognitive disorders (HAND) affect ~40% of virally suppressed people with HIV (PWH), however, the precise viral dependent and independent changes to the brain are unclear. Here we characterized the CNS reservoir and immune environment of SIV-infected (SIV+) rhesus macaques during...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2023-03-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1011290 |
| _version_ | 1797836833481031680 |
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| author | Sarah J Byrnes Kathleen Busman-Sahay Thomas A Angelovich Skyler Younger Sol Taylor-Brill Michael Nekorchuk Stephen Bondoc Rachel Dannay Margaret Terry Catherine R Cochrane Trisha A Jenkins Michael Roche Claire Deleage Steven E Bosinger Mirko Paiardini Bruce J Brew Jacob D Estes Melissa J Churchill |
| author_facet | Sarah J Byrnes Kathleen Busman-Sahay Thomas A Angelovich Skyler Younger Sol Taylor-Brill Michael Nekorchuk Stephen Bondoc Rachel Dannay Margaret Terry Catherine R Cochrane Trisha A Jenkins Michael Roche Claire Deleage Steven E Bosinger Mirko Paiardini Bruce J Brew Jacob D Estes Melissa J Churchill |
| author_sort | Sarah J Byrnes |
| collection | DOAJ |
| description | HIV-associated neurocognitive disorders (HAND) affect ~40% of virally suppressed people with HIV (PWH), however, the precise viral dependent and independent changes to the brain are unclear. Here we characterized the CNS reservoir and immune environment of SIV-infected (SIV+) rhesus macaques during acute (n = 4), chronic (n = 12) or ART-suppressed SIV infection (n = 11). Multiplex immunofluorescence for markers of SIV infection (vRNA/vDNA) and immune activation was performed on frontal cortex and matched colon tissue. SIV+ animals contained detectable viral DNA+ cells that were not reduced in the frontal cortex or the gut by ART, supporting the presence of a stable viral reservoir in these compartments. SIV+ animals had impaired blood brain barrier (BBB) integrity and heightened levels of astrocytes or myeloid cells expressing antiviral, anti-inflammatory or oxidative stress markers which were not abrogated by ART. Neuroinflammation and BBB dysfunction correlated with measures of viremia and immune activation in the gut. Furthermore, SIV-uninfected animals with experimentally induced gut damage and colitis showed a similar immune activation profile in the frontal cortex to those of SIV-infected animals, supporting the role of chronic gut damage as an independent source of neuroinflammation. Together, these findings implicate gut-associated immune activation/damage as a significant contributor to neuroinflammation in ART-suppressed HIV/SIV infection which may drive HAND pathogenesis. |
| first_indexed | 2024-04-09T15:15:17Z |
| format | Article |
| id | doaj.art-a8b2d780e7df44039d495cd700b5e282 |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-04-09T15:15:17Z |
| publishDate | 2023-03-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-a8b2d780e7df44039d495cd700b5e2822023-04-30T05:31:06ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742023-03-01193e101129010.1371/journal.ppat.1011290Chronic immune activation and gut barrier dysfunction is associated with neuroinflammation in ART-suppressed SIV+ rhesus macaques.Sarah J ByrnesKathleen Busman-SahayThomas A AngelovichSkyler YoungerSol Taylor-BrillMichael NekorchukStephen BondocRachel DannayMargaret TerryCatherine R CochraneTrisha A JenkinsMichael RocheClaire DeleageSteven E BosingerMirko PaiardiniBruce J BrewJacob D EstesMelissa J ChurchillHIV-associated neurocognitive disorders (HAND) affect ~40% of virally suppressed people with HIV (PWH), however, the precise viral dependent and independent changes to the brain are unclear. Here we characterized the CNS reservoir and immune environment of SIV-infected (SIV+) rhesus macaques during acute (n = 4), chronic (n = 12) or ART-suppressed SIV infection (n = 11). Multiplex immunofluorescence for markers of SIV infection (vRNA/vDNA) and immune activation was performed on frontal cortex and matched colon tissue. SIV+ animals contained detectable viral DNA+ cells that were not reduced in the frontal cortex or the gut by ART, supporting the presence of a stable viral reservoir in these compartments. SIV+ animals had impaired blood brain barrier (BBB) integrity and heightened levels of astrocytes or myeloid cells expressing antiviral, anti-inflammatory or oxidative stress markers which were not abrogated by ART. Neuroinflammation and BBB dysfunction correlated with measures of viremia and immune activation in the gut. Furthermore, SIV-uninfected animals with experimentally induced gut damage and colitis showed a similar immune activation profile in the frontal cortex to those of SIV-infected animals, supporting the role of chronic gut damage as an independent source of neuroinflammation. Together, these findings implicate gut-associated immune activation/damage as a significant contributor to neuroinflammation in ART-suppressed HIV/SIV infection which may drive HAND pathogenesis.https://doi.org/10.1371/journal.ppat.1011290 |
| spellingShingle | Sarah J Byrnes Kathleen Busman-Sahay Thomas A Angelovich Skyler Younger Sol Taylor-Brill Michael Nekorchuk Stephen Bondoc Rachel Dannay Margaret Terry Catherine R Cochrane Trisha A Jenkins Michael Roche Claire Deleage Steven E Bosinger Mirko Paiardini Bruce J Brew Jacob D Estes Melissa J Churchill Chronic immune activation and gut barrier dysfunction is associated with neuroinflammation in ART-suppressed SIV+ rhesus macaques. PLoS Pathogens |
| title | Chronic immune activation and gut barrier dysfunction is associated with neuroinflammation in ART-suppressed SIV+ rhesus macaques. |
| title_full | Chronic immune activation and gut barrier dysfunction is associated with neuroinflammation in ART-suppressed SIV+ rhesus macaques. |
| title_fullStr | Chronic immune activation and gut barrier dysfunction is associated with neuroinflammation in ART-suppressed SIV+ rhesus macaques. |
| title_full_unstemmed | Chronic immune activation and gut barrier dysfunction is associated with neuroinflammation in ART-suppressed SIV+ rhesus macaques. |
| title_short | Chronic immune activation and gut barrier dysfunction is associated with neuroinflammation in ART-suppressed SIV+ rhesus macaques. |
| title_sort | chronic immune activation and gut barrier dysfunction is associated with neuroinflammation in art suppressed siv rhesus macaques |
| url | https://doi.org/10.1371/journal.ppat.1011290 |
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