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 neuroAIDS 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, gp120, are taken up and transported across the BBB of the mouse. Here, we compared the ability of gp120 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 gp120 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 gp120 or HIV-1. Wheatgerm agglutinin has been previously shown to stimulate gp120 and HIV-1 uptake by the BBB; here, it stimulated the uptake of gp120 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.
Banks
William A
WA
GRECC, Veterans Affairs Medical Center--St. Louis and Saint Louis University School of Medicine, Division of Geriatrics, Department of Internal Medicine, St. Louis, MO 63106, USA. bankswa@slu.edu
Kumar
Vijaya B
VB
Franko
Mark W
MW
Bess
Julian W
JW
Arthur
Larry O
LO
D015082:2,2'-Dipyridyl / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology*; D001921:Brain / Q000821:virology; D002196:Capillaries / Q000821:virology; D002460:Cell Line; D004220:Disulfides / Q000494:pharmacology; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1; D006801:Humans; D051379:Mice; D013045:Species Specificity; D014909:Wheat Germ Agglutinins
D004220:Disulfides; D015699:HIV Envelope Protein gp120; D014909:Wheat Germ Agglutinins; C001105:2,2'-dipyridyl disulfide; D015082:2,2'-Dipyridyl