Altered T cell surface glycosylation in HIV-1 infection results in increased susceptibility to galectin-1-induced cell death |
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Authors: | Lantéri Marion Giordanengo Valérie Hiraoka Nobuyoshi Fuzibet Jean-Gabriel Auberger Patrick Fukuda Minoru Baum Linda G Lefebvre Jean-Claude |
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Affiliation: | INSERM U526, Laboratoire de Virologie, Faculté de Médecine, avenue de Valombrose, 06107 Nice Cedex 2, France. |
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Abstract: | The massive T cell death that occurs in HIV type 1 (HIV-1) infection contributes profoundly to the pathophysiology associated with AIDS. The mechanisms controlling cell death of both infected and uninfected T cells ("bystander" death) are not completely understood. We have shown that HIV-1 infection of T cells results in altered glycosylation of cell surface glycoproteins; specifically, it decreased sialylation and increased expression of core 2 O-glycans. Galectin-1 is an endogenous human lectin that recognizes these types of glycosylation changes and induces cell death of activated lymphocytes. Therefore we studied the possible contribution of galectin-1 in the pathophysiology of AIDS. O-glycan modifications were investigated on peripheral lymphocytes from AIDS patients. Oligosaccharides from CD43 and CD45 of CEM cells latently infected with HIV-1 were chemically analyzed. Consistent with our previous results, we show that HIV-1 infection results in accumulation of exposed lactosamine residues, oligosaccharides recognized by galectin-1 on cell surface glycoproteins. Both latently HIV-1-infected T cell lines and peripheral CD4 and CD8 T cells from AIDS patients exhibited exposed lactosamine residues and demonstrated marked susceptibility to galectin-1-induced cell death, in contrast to control cultures or cells from uninfected donors. The fraction of cells that died in response to galectin-1 exceeded the fraction of infected cells, indicating that death of uninfected cells occurred. Altered cell surface glycosylation of T cells during HIV-1 infection increases the susceptibility to galectin-1-induced cell death, and this death pathway can contribute to loss of both infected and uninfected T cells in AIDS. |
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Keywords: | cell death / core 2 O-glycan / lactosa-mine / poly-N-acetyllactosamine / T cells |
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