Altered sialylation of CD45 in HIV-1-infected T lymphocytes.
Immunodeficiency caused by HIV infection probably results from profound dysregulation of normal T lymphocyte properties by the virus. Despite description of the virus cytopathicity and numerous modifications in T cell functions, such as perturbation of antigen receptor signaling, CD4 downregulation, and induction of apoptosis, the precise mechanisms underlying the disruption of normal immune responses have not yet been elucidated. In the present study, we show that HIV-1-infected lymphocytes of the CEM cell line (either latent or virus-producing) and HIV-1-infected CD4+ lymphocytes have several membrane proteins with altered glycosylation patterns. Using lectins with specificity for different carbohydrate moieties, we could demonstrate the presence of two exposed nonsialylated disaccharides: a terminal Gal beta 1-->3GalNAc and a terminal Gal beta 1-->4GlcNAc. In particular, CD45, one of the major T cell glycoproteins, appeared to be partially sialylated on N- and O-linked carbohydrate moieties. Concerning the latter, PNA lectin which recognizes nonsialylated terminal Gal beta 1-->3GalNAc might precipitate up to 75% of the total tyrosine phosphatase activity displayed by CD45 molecules from one latently HIV-1-infected CEM cell line. Since CD45 glycoproteins are thought to play an important regulatory role in cell-to-cell interactions owing to their variable extracellular region and because they may regulate membrane signaling through their intracellular phosphatase domains, we suggest that these altered CD45 molecules may present an abnormal signal for natural ligands such as the B-cell-specific surface receptor CD22, thus perturbing the normal immune response in HIV-1-infected individuals.
Lefebvre
J C
JC
Laboratoire de Virologie, U.E.R. de Médecine, Nice, France.
Giordanengo
V
V
Doglio
A
A
Cagnon
L
L
Breittmayer
J P
JP
Peyron
J F
JF
Lesimple
J
J
D002240:Carbohydrate Sequence; D002478:Cells, Cultured; D006031:Glycosylation; D015497:HIV-1; D017493:Leukocyte Common Antigens / Q000096:biosynthesis* / Q000378:metabolism; D008969:Molecular Sequence Data; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D012795:Sialoglycoproteins / Q000096:biosynthesis* / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism* / Q000382:microbiology*
D012795:Sialoglycoproteins; D017493:Leukocyte Common Antigens; D017027:Protein Tyrosine Phosphatases