CD9 clustering and formation of microvilli zippers between contacting cells regulates virus-induced cell fusion.
Members of the tetraspanin family including CD9 contribute to the structural organization and plasticity of the plasma membrane. K41, a CD9-specific monoclonal antibody, inhibits the release of HIV-1 and canine distemper virus (CDV)- but not measles virus (MV)-induced cell-cell fusion. We now report that K41, which recognizes a conformational epitope on the large extracellular loop of CD9, induces rapid relocation and clustering of CD9 in net-like structures at cell-cell contact areas. High-resolution analyses revealed that CD9 clustering is accompanied by the formation of microvilli that protrude from either side of adjacent cell surfaces, thus forming structures like microvilli zippers. While the cellular CD9-associated proteins beta(1)-integrin and EWI-F were co-clustered with CD9 at cell-cell interfaces, viral proteins in infected cells were differentially affected. MV envelope proteins were detected within CD9 clusters, whereas CDV proteins were excluded from CD9 clusters. Thus, the tetraspanin CD9 can regulate cell-cell fusion by controlling the access of the fusion machinery to cell contact areas.
Singethan
Katrin
K
Institute for Virology and Immunobiology, University of Würzburg, Versbacher Str. 7, D-97078 Würzburg, Germany.
Müller
Nora
N
Schubert
Sabine
S
Lüttge
Doreen
D
Krementsov
Dimitry N
DN
Khurana
Sandhya R
SR
Krohne
Georg
G
Schneider-Schaulies
Sibylle
S
Thali
Markus
M
Schneider-Schaulies
Jürgen
J
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D000914:Antibodies, Viral / Q000276:immunology / Q000648:ultrastructure; D015703:Antigens, CD / Q000276:immunology* / Q000378:metabolism / Q000648:ultrastructure; D016466:CHO Cells; D002450:Cell Communication; D002459:Cell Fusion; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D006224:Cricetinae; D003412:Cricetulus; D004217:Distemper Virus, Canine / Q000235:genetics / Q000472:pathogenicity*; D004285:Dogs; D042783:Endothelial Cells / Q000276:immunology / Q000648:ultrastructure / Q000821:virology; D004730:Endothelium, Vascular / Q000166:cytology; D019084:Fluorescent Antibody Technique, Indirect; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D008459:Measles virus / Q000235:genetics / Q000472:pathogenicity*; D008562:Membrane Glycoproteins / Q000276:immunology* / Q000378:metabolism / Q000648:ultrastructure; D008871:Microvilli / Q000378:metabolism* / Q000648:ultrastructure; D060245:Tetraspanin 29; D014162:Transfection; D014471:Umbilical Veins / Q000166:cytology; D014709:Vero Cells
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D015703:Antigens, CD; C554869:CD9 protein, human; D008562:Membrane Glycoproteins; D060245:Tetraspanin 29