Abstract
A neuroinvasive/neuropathogenic SIV variant termed SIVmac182 was previously isolated and characterized (Watry et al, 1994). This neuroinvasive strain was derived from the uncloned strain SIVmac251 through serial animal passage of infected microglia, unlike previously reported neurovirulent strains. Importantly, the virus described here was isolated from a strain which already demonstrates limited neuroinvasiveness in vivo, through a route of inoculation which exerts selective pressure for variants in the periphery that can naturally cross the blood-brain barrier and gain access to the brain. Examination of animal tissues indicated that the neuroinvasive strain was capable of replicating in brain microvascular endothelial cells (BMEC). Therefore, we developed an in vitro model of BMEC infection in which to examine mechanisms of virus neuroinvasiveness and neuropathogenicity as well as to address mechanisms of HIV-induced dementia. Results obtained with this in vitro system indicate that growth in BMEC may predict neuroinvasiveness in vivo, and furthermore, that brain passage of virus results in the generation of neuroinvasive strains which demonstrate an increased efficiency of BMEC infection in vitro.
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