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

Life Sci. 2005 Sep 23;77(19):2361-8. doi: 10.1016/j.lfs.2004.11.041.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 2,2'-Dipyridyl / analogs & derivatives
  • 2,2'-Dipyridyl / pharmacology
  • Animals
  • Blood-Brain Barrier / physiology*
  • Brain / virology
  • Capillaries / virology
  • Cell Line
  • Disulfides / pharmacology
  • HIV Envelope Protein gp120 / metabolism
  • HIV Infections / virology*
  • HIV-1*
  • Humans
  • Mice
  • Species Specificity
  • Wheat Germ Agglutinins

Substances

  • Disulfides
  • HIV Envelope Protein gp120
  • Wheat Germ Agglutinins
  • 2,2'-dipyridyl disulfide
  • 2,2'-Dipyridyl