AIDSWEEKLY Plus; December 9, 2002
Michael Greer, Senior Medical Writer

"The capacity of the HIV-1 envelope glycoprotein gp120 to induce intracellular signals is thought to contribute to HIV-1 pathogenesis," according to Sandrina Kinet and colleagues at the National Center for Scientific Research in Montpellier, France and the University of Iowa in Iowa City.

These virus-induced signals could be transmitted by activated CD4 cells, but not by their quiescent counterparts, Kinet and coauthors found.

CD4 cells prestimulated through the T-cell receptor (TCR) set off the mitogen-activated protein kinase (MAPK) signaling cascade after binding to gp120, the researchers said. The MAPK signaling pathway remained closed when gp120 bound to quiescent or nonproliferating cells, however, despite normal gp120 receptor expression by these cells.

TCR-stimulated T cells upregulated GM1, a ganglioside that marks the presence of lipid rafts, according to the report. Other studies have found evidence that glycosphingolipids in raft microdomains can facilitate HIV-cell fusion, essentially acting as HIV coreceptors like CXCR4 and CD4.

Interfering with viral lipid raft activity suppressed gp120-induced MAPK signaling (gp120-Mediated induction of the MAPK cascade is dependent on the activation state of CD4+ lymphocytes. Blood 2002 Oct 1;100(7):2546-53.

"Thus, stimulation of a mitogenic pathway by gp120 appears to require receptor binding in the context of membrane microdomains," Kinet and colleagues concluded. "These studies reveal a mechanism via which gp120 may differentially modulate the fate of activated and quiescent T cells in vivo."

The corresponding author for this report is Naomi Taylor, Institut de Genetique Moleculaire de Montpellier, CNRS UMR 5535, IFR 22, 1919 route Mende, F-34293 Montpellier 5, France. E-mail: taylor@jones.igm.cnrs-mop.fr.

Key points reported in this study include:

• HIV gp120-induced cell signaling requires activated CD4 cells

• Quiescent or nonproliferating cells failed to activate mitogen-activated protein kinase (MAPK) after gp120 binding

• Cells activated through the T-cell receptor upregulated markers of lipid rafts, which may be involved in gp120-induced signaling

This article was prepared by AIDS Weekly editors from staff and other reports.

Reference

Kinet S, Bernard F, Mongellaz C, et al., "gp120-mediated induction of the MAPK cascade is dependent on the activation state of CD4(+) lymphocytes", Blood 2002 Oct 1;100(7):2546-53

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