Circulating gp120 alters the blood-brain barrier permeability in HIV-1 gp120 transgenic mice.

The mechanism underlying invasion of the central nervous system by HIV-1 is unclear. We recently demonstrated blood-brain barrier changes in a model of HIV-1 gp120 transgenic mice. To test whether this alteration was intrinsic to the brain endothelium of transgenic mice or depended on circulating gp120, we used brain endothelial cultures from gp120 transgenic and non-transgenic mice and exposed them to serum from gp120 transgenic or non-transgenic mice. We measured permeability to albumin as a marker of functional endothelial integrity. A significant increase in permeability (up to 47%) was observed in transgenic and non-transgenic cultures exposed to serum samples from transgenic but not to those from non-transgenic mice. This permeability was neutralized after immunoabsorption of sera with anti-gp120 monoclonal antibody. These findings demonstrate that the blood-brain barrier alteration in HIV-1 gp120 transgenic mice is due to circulating gp120.