Cell-to-cell contact via measles virus haemagglutinin-CD46 interaction triggers CD46 downregulation.
CD46 downregulation by measles virus (MV) occurs after expression of virus haemagglutinin (H) protein on the surface of the infected cell and is a consequence of CD46-H interaction on the cell membrane. To assess whether CD46 downregulation also occurs after CD46-H interaction when these two molecules are expressed on distinct cells, we used human T cell line Jurkat (expressing CD46) and transfected murine fibroblast line L stably expressing MV-H protein (L.H). FACS analysis shows that cell-to-cell contact of 1 h at 37 degrees C triggers a reduction of CD46 cell surface labelling as detected by MCI20.6, GB24 and J4-48 monoclonal antibodies. This reduction is similar to that observed after MV infection or after infection with recombinant vaccinia virus encoding MV-H protein. By contrast, MV-H protein was downregulated only when CD46-H interaction occurred on the same cell membrane. CD46 downregulation is specific for CD46-H interaction because it was not observed after coincubation of Jurkat cells with either L cells expressing MV nucleoprotein (L.NP) or L cells. Moreover, this downregulation could be blocked by either anti-CD46 or anti-H antibodies. The H-mediated CD46 downregulation is reversible and restricted to CD46 since expression of other surface markers (CD3, CD14, CD47 and CD63) is unaffected. It is apparently not mediated in a protein kinase (PK) A- or PKC-dependent manner. Altogether, our results provide an unequivocal demonstration that interaction between the extracellular domains of CD46 and MV-H is sufficient to trigger CD46 downregulation.
Krantic
S
S
Laboratoire de Biologie Moléculaire et Cellulaire, Ecole Normale Supérieure, Lyon, France.
Gimenez
C
C
Rabourdin-Combe
C
C
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D000914:Antibodies, Viral / Q000378:metabolism; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism*; D003994:Bucladesine / Q000494:pharmacology; D002450:Cell Communication; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D015536:Down-Regulation; D004789:Enzyme Activation; D006389:Hemagglutinins, Viral / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D008459:Measles virus / Q000502:physiology*; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D051379:Mice; D010726:Phosphodiesterase Inhibitors; D011493:Protein Kinase C / Q000378:metabolism; D011991:Receptors, Virus / Q000276:immunology / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000914:Antibodies, Viral; D015703:Antigens, CD; C497857:CD46 protein, human; D006389:Hemagglutinins, Viral; C497859:Mcp protein, mouse; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D010726:Phosphodiesterase Inhibitors; D011991:Receptors, Virus; C032397:hemagglutinin protein G, measles virus; D005576:Colforsin; C020922:4-O-methyl-12-O-tetradecanoylphorbol 13-acetate; D003994:Bucladesine; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D015056:1-Methyl-3-isobutylxanthine