Elsevier

Life Sciences

Volume 61, Issue 9, 25 July 1997, Pages PL119-PL125
Life Sciences

Pharmacology letter Accelerated communication
HIV-1 protein gp120 crosses the blood-brain barrier: Role of adsorptive endocytosis

https://doi.org/10.1016/S0024-3205(97)00597-3Get rights and content

Abstract

HIV-1 infects the brain and leads to AIDS dementia complex. The viral coat glycoprotein, gp120, may facilitate the passage of HIV-1 and HIV-infected immune cells across the blood-brain barrier (BBB). Since the endothelial cells of the BBB do not possess the CD4 or galactosylceramide binding sites used by gp120 to induce HIV-1 uptake into other cell types, how gp120 mediates entry into brain is unknown. We postulate that gp120 crosses the BBB and does so by acting as a weak lectin to induce adsorptive endocytosis (AE) in a fashion similar to other glycoproteins like wheatgerm agglutinin (WGA). We found in vivo that gp120 crosses the BBB and its passage is enhanced 18.7-fold by WGA. In vitro studies confirm that WGA enhances uptake of gp120 by brain endothelia; most of the uptake is membrane-associated, as expected in AE. Uptake is not dependent on clatharin, caveolae, calcium channels, or endosomal acidification. Our results suggest that gp120 crosses the BBB and does so by acting as a lectin to induce AE.

References (29)

  • I. Elovaara et al.

    J. Neurol. Sci.

    (1987)
  • A.V. Moses et al.

    Adv. Neuroimmunol.

    (1994)
  • A.A. Hurwitz et al.

    Adv. Neuroimmunol.

    (1994)
  • R.D. Broadwell et al.

    Exp. Neurol.

    (1993)
  • A.S. Lossinsky et al.

    Microvasc. Res.

    (1991)
  • E.G. Gutierrez et al.

    J. Neuroimmunol.

    (1993)
  • D.Z. Gerhart et al.

    Brain Res. Bull.

    (1988)
  • G.P. Smith et al.

    Peptides

    (1981)
  • V.P. Knutson et al.

    J. Biol. Chem.

    (1983)
  • A. Tsuji et al.

    Life Sci.

    (1992)
  • C.A. Wiley et al.
  • R. Masereeuw et al.

    Pharm. Res.

    (1994)
  • A.V. Moses et al.
  • R.D. Broadwell et al.
  • Cited by (0)

    View full text