Latent HIV Infection of BBB Pericytes Enhances Gap Junction-mediated Crosstalk with Endothelial Cells
Year: 2026
Type: article
Abstract: HIV-Associated Neurocognitive Impairments persist, with over 50% of patients experiencing cognitive decline. 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 days, 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.
Source: Molecular Neurobiology
Language: English
Subfield: Neurology
Field: Neuroscience
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,590
Funders: University of Miami, Sylvester Comprehensive Cancer Center, University of Miami Health Systems, National Institutes of Health, National Heart, Lung, and Blood Institute, National Institute of Mental Health, National Institute on Drug Abuse, National Cancer Institute, National Institute of Neurological Disorders and Stroke, National Institute of Environmental Health Sciences
Awards: G1056143923, G130322559, G1353012146, G1910588693, G2461854243, Role of cerebral vasculature in brain ischemia in HIV infection, G305175183, California NeuroAIDS Tissue Network, G3358011790, G3471390838, G3550442147, G3758901989, NNTC Data Coordinating Center, G427533880, The Manhattan HIV Brain Bank, G4559771646, Texas NeuroAIDS Research Center, NATIONAL NEUROLOGICAL AIDS BANK, Targeting Inflammasomes in Substance Abuse and HIV, G849610127, CCL2/CCR2 modulates HIV-associated ischemic stroke by regulating blood brain barrier monocyte recruitment, G897712522, G9000038791, G9000068970, G9000117651, G9000184170, G9000277646, Impact of miRNAs on adult neurogenesis following exposure to methamphetamine and HIV-1 Infection, HIV-1 and amyloid beta interactions at the blood-brain barrier, Defining brain pericytes as a novel and myeloid-derived HIV reservoir, The Sylvester Cancer Center Support Grant, Inflammasome Activation and Gut-Brain Axis Dysregulation in HIV and Methamphetamine-Associated Depression, Adolescent exposure to PCBs as a risk factor for the development of depression
OpenAlex ID: W7202275380