HIV-1 viral protein effect on cerebral microvasculature: an in vitro blood–brain barrier model
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Date
2025
Journal Title
Journal ISSN
Volume Title
Publisher
American Physiological Society
Abstract
The 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.
Description
Keywords
Blood–Brain Barrier, Human Immunodeficiency Virus, Trans Endothelial Electrical Resistance, Central Nervous System, Cerebrovascular Disease
Citation
Matubatuba, 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.