Evidence that the species barrier of human immunodeficiency virus-1 does not extend to uptake by the blood-brain barrier: Comparison of mouse and human brain microvessels

HIV-1 within the CNS produces a neuroAlDS syndrome and may act as a reservoir for reinfection of the peripheral tissues. Study of how HIV-1 crosses the blood-brain barrier (BBB) has been hampered by the lack of nonprimate animal models. However, BBB transport of HIV-1 does not involve any of the known steps conferring species specificity, including binding to CD4 receptors. In vivo and in vitro studies show that HIV-1 and its glycoprotein coat, gp 120, are taken up and transported across the BBB of the mouse. Here, we compared the ability of gp 120 and HIV-1 to be taken up by isolated brain microvessels (IBM) freshly isolated from mice, from post-mortem human brain, and from mice that had been treated in a manner analogous to the human material (mouse post-mortem). Freshly isolated mouse IBM took up more gp 120 and HIV-1 than the human or mouse post-mortem cells. We found no difference between the ability of mouse post-mortem and human IBM to take up either gp 120 or HIV-1 . Wheatgerm agglutinin has been previously shown to stimulate gp 120 and HIV-1 uptake by the BBB; here, it stimulated the uptake of gp 120 and of HIV-1 by both mouse post-mortem and human IBM, although stimulated uptake was greatest for fresh mouse IBM. These results show that the mouse can be used to study the initial phases of HIV-1 uptake by the BBB. Published by Elsevier Inc.