EFFICIENT INFECTION OF BRAIN MICROVASCULAR ENDOTHELIAL-CELLS BY AN INVIVO-SELECTED NEUROINVASIVE SIVMAC VARIANT

A neuroinvasive/neuropathogenic SIV variant termed SIV(mac)182 was pre viously isolated and characterized (Watry et al, 1994). This neuroinva sive strain was derived from the uncloned strain SIV(mac)251 through s erial animal passage of infected microglia, unlike previously reported neurovirulent strains. Importantly, the virus described here was isol ated from a strain which already demonstrates limited neuroinvasivenes s in vivo, through a route of inoculation which exerts selective press ure for variants in the periphery that can naturally cross the blood-b rain barrier and gain access to the brain. Examination of animal tissu es indicated that the neuroinvasive strain was capable of replicating in brain microvascular endothelial cells (BMEC). Therefore, we develop ed an in vise model of BMEC infection in which to examine mechanisms o f virus neuroinvasiveness and neuropathogenicity as well as to address mechanisms of HIV-induced dementia. Results obtained with this in vit ro system indicate that growth in BMEC may predict neuroinvasiveness i n vivo, and furthermore, that brain passage of virus results in the ge neration of neuroinvasive strains which demonstrate an increased effic iency of BMEC infection in vitro.