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Blood-brain barrier (BBB) impairment is a consistent feature of this comorbidity, which is remarkable, because BBB endothelial cells are not productively infected by HIV-1. Conversely, pericytes can be productively infected with HIV-1 and are essential for cerebrovascular homeostasis. Given this, we hypothesized that HIV-1 infection of pericytes disrupts BBB endothelial cell integrity through dysfunctional gap junction and hemichannel signaling, impairing pericyte-endothelial intercellular communication. Using a co-culture model with primary human BBB pericytes and brain microvascular endothelial cells, pericytes were infected with HIV-1 for 3 or 7\u00a0days, exhibiting active and latent viral phenotypes. Findings revealed enhanced gap junction communication between HIV-infected pericytes and endothelial cells under both conditions, and blocking gap junctions modulated endothelial inflammatory responses. Overall, this study advances our understanding of the molecular mechanisms underlying HIV-associated BBB dysfunction and may inform the development of targeted therapeutic strategies.<\/jats:p>","DOI":"10.1007\/s12035-026-06266-0","type":"journal-article","created":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T09:13:40Z","timestamp":1792142020000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Latent HIV Infection of BBB Pericytes Enhances Gap Junction-mediated Crosstalk with Endothelial Cells"],"prefix":"10.1007","volume":"63","author":[{"given":"Sarah","family":"Schmidlin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oandy","family":"Naranjo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Torices","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolai","family":"Fattakhov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Gilicinska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masha","family":"Minevich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyra A.","family":"Schindler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Destiny","family":"Tiburcio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia M.","family":"Osborne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arpan","family":"Acharya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minseon","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Stevenson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siddappa N.","family":"Byrareddy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michal","family":"Toborek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,16]]},"reference":[{"key":"6266_CR1","doi-asserted-by":"publisher","first-page":"102503","DOI":"10.1016\/j.ebiom.2019.10.029","volume":"51","author":"S Velasquez","year":"2020","unstructured":"Velasquez S, Prevedel L, Valdebenito S, Gorska AM, Golovko M, Khan N, Geiger J, Eugenin EA (2020) Circulating levels of ATP is a biomarker of HIV cognitive impairment. 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