{"doi":"10.1093/brain/awaf262","title":"Occludin modulates HIV and ischaemic stroke response via the mitochondrial antiviral signalling pathway","abstract":"Specific cell types of the blood-brain barrier (BBB), such as pericytes, can be infected by HIV-1. Importantly, alterations of the expression of tight junction protein occludin (OCLN) have been linked to regulation of HIV-1 infection. In the present study, we hypothesized that OCLN can influence HIV-1 infection via modulating innate immunity responses. Unbiased transcriptome analysis was conducted on wild-type and OCLN-silenced primary human BBB pericytes. The role of differentially expressed innate-immunity pathways was then evaluated in the context of mitochondrial dysfunction and HIV-1 infection. Using a model of ischaemic stroke and OCLN-deficient mice, we elucidated the functional role of OCLN in cerebrovascular health in the presence of HIV-1 infection. OCLN silencing resulted in alterations of the gene expression signatures of interferon-stimulated genes and the antiviral retinoic acid-inducible gene-1 (RIG-I) pathway, which functions as a regulator of the cytoplasmic sensors upstream of the mitochondrial antiviral signalling protein. Indeed, we observed dysfunctional mitochondrial bioenergetics, dynamics and autophagy following OCLN silencing. Alterations of mitochondrial bioenergetics and innate immune protection translated into worsened ischaemic stroke outcomes in EcoHIV-infected OCLN-deficient mice. Animal studies also confirmed that OCLN-/- mice had higher EcoHIV load in plasma, spleen and brain. Our results allow for a better understanding of the molecular mechanisms of viral infection in the brain and describe a previously unrecognized role of occludin as a key factor in the control of innate immune responses and mitochondrial dynamics at the BBB level, which influence cerebral vascular disease outcomes such as ischaemic stroke.","journal":"Brain","year":2025,"id":532670,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9602,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1333566,"name":"T Lázaro Moreno","orcid":null,"position":1,"is_corresponding":false},{"id":254214,"name":"Olivia Osborne","orcid":"0000-0002-8289-8429","position":2,"is_corresponding":false},{"id":863190,"name":"Sita Ramaswamy","orcid":"0000-0003-1479-6954","position":3,"is_corresponding":false},{"id":653097,"name":"Oandy Naranjo","orcid":"0000-0002-4223-6869","position":4,"is_corresponding":false},{"id":653098,"name":"Tímea Téglás","orcid":"0000-0003-4565-3315","position":5,"is_corresponding":false},{"id":1333211,"name":"Minseon Park","orcid":"0000-0001-5709-2522","position":6,"is_corresponding":false},{"id":1073973,"name":"Enze Sun","orcid":"0009-0007-3508-1874","position":7,"is_corresponding":false},{"id":254218,"name":"Michał Toborek","orcid":"0000-0003-4475-2119","position":8,"is_corresponding":false},{"id":653096,"name":"Silvia Torices","orcid":"0000-0001-8979-887X","position":0,"is_corresponding":true}],"reference_count":115,"raw_metadata":null,"created_at":"2026-07-19T02:51:27.893975Z","pmid":"40663632","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":[]}