Adsorptive endocytosis of HIV-1gp120 by blood-brain barrier is enhanced bylipopolysaccharide

Previous work suggests that gp120 mediates the passage of HIV-1 and infecte d immune cells across the blood-brain barrier (BBB) by induction of adsorpt ive endocytosis (AE) in brain endothelial cells. Other work has suggested t hat cytokines may increase the permeability of the BBB to free virus or inf ected immune cells. Here, we investigated the ability of lipopolysaccharide (LPS), a bacterial wall toxin that stimulates the release of cytokines, to increase gp120 passage across the BBB by enhancement of AE and/or inductio n of BBB disruption, We found that LPS enhanced the passage of gp120 radioa ctively labeled with I-125 (I-gp120) in a reversible, time-dependent, prost aglandin-independent manner that was not completely explained by disruption of the BBB. LPS also enhanced wheatgerm agglutinin mediated uptake of I-gp 120 almost exclusively through the potentiation of AE, These results show t hat LPS or cytokines released by LPS can have a major effect on the permeab ility of the BBB to HIV-1gp120 both by stimulating AE and by inducing a dis ruption of the BBB. This suggests that bacterial infection or other inflamm atory states could facilitate invasion of the CNS by HIV-1.