Synergistic inhibition in cell-cell fusion mediated by the matrix and nucleocapsid protein of canine distemper virus.
Canine distemper virus (CDV) causes a chronic, demyelinating, progressive or relapsing neurological disease in dogs, because CDV persists in the CNS. Persistence of virulent CDV, such as the A75/17 strain has been reproduced in cell cultures where it is associated with a non-cytolytic infection with very limited cell-cell fusion. This is in sharp contrast to attenuated CDV infection in cell cultures, such as the Onderstepoort (OP) CDV strain, which produces extensive fusion activity and cytolysis. Fusion efficiency may be determined by the structure of the viral fusion protein per se but also by its interaction with other structural proteins of CDV. This was studied by combining genes derived from persistent and non-persistent CDV strains in transient transfection experiments. It was found that fusion efficiency was markedly attenuated by the structure of the fusion protein of the neurovirulent A75/17-CDV. Moreover, we showed that the interaction of the surface glycoproteins with the M protein of the persistent strain greatly influenced fusion activity. Site directed mutagenesis showed that the c-terminus of the M protein is of particular importance in this respect. Interestingly, although the nucleocapsid protein alone did not affect F/H-induced cell-cell fusion, maximal inhibition occurred when the latter was added to combined glycoproteins with matrix protein. Thus, the present study suggests that very limited fusogenicity in virulent CDV infection, which favours persistence by limiting cell destruction involves complex interactions between all viral structural proteins.
Wiener
Dominique
D
Department of Clinical Veterinary Medicine, University of Bern, Bremgartenstrasse 109a, 3001Bern, Switzerland.
Plattet
Philippe
P
Cherpillod
Pascal
P
Zipperle
Ljerka
L
Doherr
Marcus G
MG
Vandevelde
Marc
M
Zurbriggen
Andreas
A
D000818:Animals; D002459:Cell Fusion; D002522:Chlorocebus aethiops; D004217:Distemper Virus, Canine / Q000235:genetics / Q000378:metabolism; D004285:Dogs; D008561:Membrane Fusion; D019590:Nucleocapsid Proteins / Q000378:metabolism*; D014709:Vero Cells; D014760:Viral Fusion Proteins / Q000378:metabolism; D014763:Viral Matrix Proteins / Q000737:chemistry / Q000378:metabolism*; D015678:Viral Structural Proteins / Q000378:metabolism
D019590:Nucleocapsid Proteins; D014760:Viral Fusion Proteins; D014763:Viral Matrix Proteins; D015678:Viral Structural Proteins