CD9-dependent regulation of Canine distemper virus-induced cell-cell fusion segregates with the extracellular domain of the haemagglutinin.
Antibodies to CD9, a member of the tetraspan transmembrane-protein family, selectively inhibit Canine distemper virus (CDV)-induced cell-cell fusion. Neither CDV-induced virus-cell fusion nor cell-cell fusion induced by the closely related morbillivirus Measles virus (MV) is affected by anti-CD9 antibodies. As CDV does not bind CD9, an unknown, indirect mechanism is responsible for the observed inhibition of cell-cell fusion. It was investigated whether this effect was restricted to only one viral glycoprotein, either the haemagglutinin (H) or the fusion (F) protein, which form a fusion complex on the surface of virions and infected cells, or whether it is dependent on both in transient co-transfection assays. The susceptibility to CD9 antibodies segregates with the H protein of CDV. By exchanging portions of the H proteins of CDV and MV, it was determined that the complete extracellular domain, including the predicted stem structure (stem 1, barrel strand 1 and stem 2) and globular head domain, of the CDV-H protein mediates the effect. This suggests that interaction of the CDV-H protein with an unknown cellular receptor(s) is regulated by CD9, rather than F protein-mediated membrane fusion.
Singethan
K
K
Institut für Virologie und Immunbiologie, Versbacher Straße 7, D-97078 Würzburg, Germany.
Topfstedt
E
E
Institut für Virologie und Immunbiologie, Versbacher Straße 7, D-97078 Würzburg, Germany.
Schubert
S
S
Institut für Virologie und Immunbiologie, Versbacher Straße 7, D-97078 Würzburg, Germany.
Duprex
W P
WP
School of Biomedical Sciences, The Queen's University of Belfast, Belfast BT9 7BL, UK.
Rima
B K
BK
School of Biomedical Sciences, The Queen's University of Belfast, Belfast BT9 7BL, UK.
Schneider-Schaulies
Jürgen
J
Institut für Virologie und Immunbiologie, Versbacher Straße 7, D-97078 Würzburg, Germany.
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology* / Q000378:metabolism; D002459:Cell Fusion; D002522:Chlorocebus aethiops; D004217:Distemper Virus, Canine / Q000235:genetics / Q000472:pathogenicity*; D004285:Dogs; D015726:Giant Cells / Q000502:physiology; D008562:Membrane Glycoproteins / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D060245:Tetraspanin 29; D014162:Transfection; D014709:Vero Cells; D014764:Viral Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D015703:Antigens, CD; C554870:Cd9 protein, mouse; D008562:Membrane Glycoproteins; D060245:Tetraspanin 29; D014764:Viral Proteins