Persistent SIV infection of a blood-brain barrier model.

In order to better model HIV infection of the brain, a dynamic, in vitro model of the blood-brain barrier (the DIV-BBB) was characterized. The model was composed of simian brain microvascular endothelial cells (MVEC) cocultured with human fetal astrocytes under conditions of media flow. Simian immunodeficiency virus (SIV) was introduced into the DIV-BBB model in order to determine whether SIV infection has an effect on the blood-brain barrier (BBB). The cells of the DIV-BBB model were maintained for 127 days, during which a low permeability to sucrose developed. SIV infection of the BBB model was readily accomplished with cell-free virus. Results from ELISA for viral p27 protein, s-MAGI assays, and coculture techniques indicate that SIV productively and persistently infected the BBB model. These studies indicate that SIV can persist in MVEC without overtly compromising BBB function, and suggest that the DIV-BBB will be a highly valuable and suitable model for studies of HIV neuropathogenesis.