{"doi":"10.1371/journal.ppat.1011290","title":"Chronic immune activation and gut barrier dysfunction is associated with neuroinflammation in ART-suppressed SIV+ rhesus macaques","abstract":"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.","journal":"PLoS Pathogens","year":2023,"id":342480,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":14,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9567,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":107593,"name":"Kathleen Busman‐Sahay","orcid":"0000-0002-8549-0023","position":1,"is_corresponding":false},{"id":521058,"name":"Thomas A. Angelovich","orcid":"0000-0003-2069-0451","position":2,"is_corresponding":false},{"id":851100,"name":"Skyler Younger","orcid":"0000-0003-1821-3314","position":3,"is_corresponding":false},{"id":1059971,"name":"Sol Taylor-Brill","orcid":null,"position":4,"is_corresponding":false},{"id":107592,"name":"Michael Nekorchuk","orcid":null,"position":5,"is_corresponding":false},{"id":233341,"name":"Stephen Bondoc","orcid":"0000-0002-4303-0651","position":6,"is_corresponding":false},{"id":1079422,"name":"Rachel Dannay","orcid":null,"position":7,"is_corresponding":false},{"id":107594,"name":"Margaret Terry","orcid":"0000-0002-7260-9005","position":8,"is_corresponding":false},{"id":920486,"name":"Catherine R. Cochrane","orcid":"0000-0001-9683-8905","position":9,"is_corresponding":false},{"id":1046103,"name":"Trisha A. Jenkins","orcid":"0000-0003-0137-6643","position":10,"is_corresponding":false},{"id":521062,"name":"Michael Roche","orcid":"0000-0001-8819-0096","position":11,"is_corresponding":false},{"id":412158,"name":"Claire Deléage","orcid":"0000-0002-3507-0055","position":12,"is_corresponding":false},{"id":232942,"name":"Steven E. Bosinger","orcid":"0000-0002-2116-5061","position":13,"is_corresponding":false},{"id":244985,"name":"Mirko Paiardini","orcid":"0000-0002-7276-3600","position":14,"is_corresponding":false},{"id":483113,"name":"Bruce J. Brew","orcid":"0000-0003-0622-1392","position":15,"is_corresponding":false},{"id":95245,"name":"Jacob D. Estes","orcid":"0000-0002-9652-6394","position":16,"is_corresponding":false},{"id":521060,"name":"Melissa J. Churchill","orcid":"0000-0001-5510-7954","position":17,"is_corresponding":false},{"id":920485,"name":"Sarah J. Byrnes","orcid":"0000-0002-3580-8574","position":0,"is_corresponding":true}],"reference_count":70,"raw_metadata":null,"created_at":"2026-07-19T01:11:12.506815Z","pmid":"36989320","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}