A CD46CD[55-46] chimeric receptor, eight short consensus repeats long, acts as an inhibitor of both CD46 (MCP)- and CD150 (SLAM)-mediated cell-cell fusion induced by CD46-using measles virus.
According to their cellular receptor use, measles virus (MV) strains can be separated into two phenotypes, CD46-using and CD46-non-using. A long chimeric receptor, CD46CD[55-46], was generated from the CD46 backbone, encompassing the four short consensus repeat (SCR) domains of CD46 linked via a flexible glycine hinge to SCR1 and SCR2 of CD55, SCR3 and SCR4 of CD46 and the STP, transmembrane and cytoplasmic tail of CD46. This chimeric receptor was proficient for MV binding but deficient in mediating MV-induced cell-to-cell fusion and virus replication, possibly due to the extended distance between the MV haemagglutinin (H) binding site (CD46 SCR1-SCR2) and the cell membrane. When coexpressed with either wild-type CD46 or CD150, this fusion-incompetent receptor exerted a dominant negative effect and inhibited both cell-to-cell fusion and entry of MV with CD46-using, but not CD46-non-using, phenotype. A soluble octameric CD46-C4bpalpha exhibited similar CD46- and CD150-mediated fusion inhibition properties only against CD46-using MV. This suggests that the long CD46CD[55-46] receptor acts by sequestering incoming MV prior to its binding to the shorter functional CD46 or CD150 receptor.
Christiansen
Dale
D
Immunité et Infections Virales, VPV, CNRS-UCBL UMR 5537, Faculté de Médecine Lyon-RTH Laennec, Rue Guillaume Paradin, 69372 Lyon Cedex 08, France1.
De Sousa
Emmanuel R
ER
Immunité et Infections Virales, VPV, CNRS-UCBL UMR 5537, Faculté de Médecine Lyon-RTH Laennec, Rue Guillaume Paradin, 69372 Lyon Cedex 08, France1.
Loveland
Bruce
B
The Austin Research Institute, Heidelberg, Victoria 3084, Australia2.
Kyriakou
Peter
P
The Austin Research Institute, Heidelberg, Victoria 3084, Australia2.
Lanteri
Marc
M
The Austin Research Institute, Heidelberg, Victoria 3084, Australia2.
Wild
Fabian T
FT
INSERM U404, CERVI, 69365 Lyon Cedex 07, France3.
Gerlier
Denis
D
Immunité et Infections Virales, VPV, CNRS-UCBL UMR 5537, Faculté de Médecine Lyon-RTH Laennec, Rue Guillaume Paradin, 69372 Lyon Cedex 08, France1.
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000737:chemistry / Q000502:physiology*; D016466:CHO Cells; D006224:Cricetinae; D006023:Glycoproteins / Q000037:antagonists & inhibitors*; D007136:Immunoglobulins; D008459:Measles virus / Q000502:physiology*; D051916:Membrane Cofactor Protein; D008561:Membrane Fusion; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000502:physiology*; D008969:Molecular Sequence Data; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000502:physiology*; D020449:Repetitive Sequences, Amino Acid; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1
D015703:Antigens, CD; D006023:Glycoproteins; D007136:Immunoglobulins; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1