Willemse, ChontrelleMakhathini, Khayelihle BrianFisher, David2026-01-142026-01-142025Matubatuba, S., Willemse, C., Makhathini, K.B., Smith, C., Fisher, D. and Mentor, S., 2025. HIV‐1 viral protein effect on cerebral microvasculature: An in vitro blood–brain barrier model. Physiological Reports, 13(19), p.e70593.https://doi.org/10.14814/phy2.70593https://hdl.handle.net/10566/21697The central nervous system (CNS) serves as a sanctuary for the Human Immunodeficiency Virus (HIV), which is facilitated by HIV's ability to breach the blood–brain barrier (BBB). BBB dysfunction occurs in the earliest stages of an HIV-1 infection. The immune-privileged CNS reduces harmful inflammatory responses, detrimental to the neuronal environment. BBB disruption, however, contributes to comorbidities in HIV, like cerebrovascular disease and neurocognitive problems. A 2-dimensional in vitro BBB model was employed to assess the effect of HL2/3 cell paracrine factors on select physiological parameters: cell proliferation, viability, toxicity, suppression, and morphology. BBB integrity was assessed using trans endothelial electrical resistance measurements. The study utilized immortalized mouse brain endothelial cell monocultures and co-cultures with the HL2/3 cell line, emulating an in vivo HIV-1 effect on the BBB.A concentration- dependent decline in cellular proliferation rates and viability was observed upon exposure to HL2/3 paracrine factors. Moreover, an elevation in cellular suppression, cell death, and cell toxicity was observed. Permeability studies confirmed decreased permeability after exposure to HIV-1 viral proteins in select in vitro BBB model systems. The impact of HIV viral proteins on brain capillary endothelium is critical to elucidate pathogen-induced cerebrovascular disease progression and vascular cognitive impairment in patients.enBlood–Brain BarrierHuman Immunodeficiency VirusTrans Endothelial Electrical ResistanceCentral Nervous SystemCerebrovascular DiseaseArticle