HIV-1 envelope glycoprotein gp120 does not bind to galactosylceramide-expressing rat oligodendrocytes.
It may be postulated that the encephalopathy induced by the human immunodeficiency virus HIV-1, in particular, the characteristic "myelin pallor," may result from binding of the envelope glycoprotein gp120 to galactosylceramide and/or its metabolite sulfatide in the plasma membrane of oligodendrocytes, the myelin forming cells in the central nervous system. (1) gp120 has been reported to have a high affinity for these molecules in vitro. (2) The binding of antibodies to these molecules increases intracellular free calcium levels, which may be cytotoxic. (3) The binding of gp120 to the CD4 receptor in the immune system has the same effect. We have investigated the binding of gp120 to rat oligodendrocytes in vitro by indirect immunofluorescence and have monitored changes in intracellular free calcium with the calcium-sensitive dye INDO-1, in individual oligodendrocytes exposed to the glycoprotein. Antibodies against galatosylceramide and sulfatide bound to the cell membrane, but gp120 did not. The antibodies also increased intracellular free calcium levels in the oligodendrocytes, whereas gp120 did not. It, therefore, seems highly improbable that the demyelination observed during HIV encephalopathy is a direct cytotoxic effect of gp120 on oligodendrocytes.
Laboratoire de Neurobiologie Cellulaire, Moléculaire et Clinique, INSERM U, 134, Paris, France.
E
E
Parmantier
M
M
Monge
M
M
Yagello
F
F
Cabon
C
C
Demerens
J C
JC
Gluckman
B
B
Zalc
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000166:cytology / Q000378:metabolism / Q000821:virology; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D005434:Flow Cytometry; D005699:Galactosylceramides / Q000096:biosynthesis*; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism*; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism* / Q000821:virology*; D011485:Protein Binding; D051381:Rats; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism / Q000821:virology
D005699:Galactosylceramides; D015699:HIV Envelope Protein gp120; D002118:Calcium