title: Altered T cell surface glycosylation in HIV-1 infection results in increased susceptibility to galectin-1-induced cell death.
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.
authors.affiliation: INSERM U526, Laboratoire de Virologie, Faculté de Médecine, avenue de Valombrose, 06107 Nice Cedex 2, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Lantéri
authors.forename: Valérie
authors.initials: V
authors.lastname: Giordanengo
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Hiraoka
authors.forename: Jean-Gabriel
authors.initials: JG
authors.lastname: Fuzibet
authors.forename: Patrick
authors.initials: P
authors.lastname: Auberger
authors.forename: Minoru
authors.initials: M
authors.lastname: Fukuda
authors.forename: Linda G
authors.initials: LG
authors.lastname: Baum
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Lefebvre
mesh_terms: D000606:Amino Sugars / Q000378:metabolism; D015703:Antigens, CD / Q000187:drug effects / Q000276:immunology; D017209:Apoptosis; D016923:Cell Death; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004229:Dithiothreitol / Q000494:pharmacology; D037483:Galectin 1 / Q000276:immunology / Q000494:pharmacology*; D006023:Glycoproteins / Q000378:metabolism; D006031:Glycosylation; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D006801:Humans; D017493:Leukocyte Common Antigens / Q000187:drug effects / Q000276:immunology; D051917:Leukosialin; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D009844:Oligosaccharides / Q000032:analysis; D011134:Polysaccharides / Q000378:metabolism; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D012795:Sialoglycoproteins / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
chemical_list: D000606:Amino Sugars; D015703:Antigens, CD; D037483:Galectin 1; D006023:Glycoproteins; D051917:Leukosialin; D009844:Oligosaccharides; D011134:Polysaccharides; C465014:SPN protein, human; D012795:Sialoglycoproteins; C066929:polylactosamine; D017493:Leukocyte Common Antigens; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D019158:N-Acetylneuraminic Acid; D004229:Dithiothreitol