Details

Autor(en) / Beteiligte

• Byrnes, Sarah J
• Busman-Sahay, Kathleen
• Angelovich, Thomas A
• Younger, Skyler
• Taylor-Brill, Sol
• Nekorchuk, Michael
• Bondoc, Stephen
• Dannay, Rachel
• Terry, Margaret
• Cochrane, Catherine R
• Jenkins, Trisha A
• Roche, Michael
• Deleage, Claire
• Bosinger, Steven E
• Paiardini, Mirko
• Brew, Bruce J
• Estes, Jacob D
• Churchill, Melissa J
• Douek, Daniel C.

Titel

Chronic immune activation and gut barrier dysfunction is associated with neuroinflammation in ART-suppressed SIV+ rhesus macaques

Ist Teil von

• PLoS pathogens, 2023-03, Vol.19 (3), p.e1011290

Ort / Verlag

United States: Public Library of Science

Erscheinungsjahr

2023

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.