HIV-1 viral protein effect on cerebral microvasculature: An in vitro blood-brain barrier model

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 transendothelial 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 impermeability 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.