Article

Caspase-mediated cleavage of the feline calicivirus capsid protein.

School of Biomedical and Life Sciences, University of Surrey, Guildford, Surrey GU2 7XH, UK.
Journal of General Virology (impact factor: 3.36). 06/2003; 84(Pt 5):1237-44. pp.1237-44
Source: PubMed

ABSTRACT Feline calicivirus (FCV) is responsible for an acute upper respiratory tract disease in cats. The FCV capsid protein is synthesized as a precursor (76 kDa) that is post-translationally processed into the mature 62 kDa capsid protein by removal of the N-terminal 124 amino acids. Our previous studies have also detected a 40 kDa protein, related to the FCV capsid protein, produced during infection. Here we demonstrate that cleavage of the FCV capsid protein, during infection of cells in culture, was prevented by caspase inhibitors. In addition, caspase-2, -3 and -7 were activated during FCV infection, as shown by pro-form processing, an increase in N-acetyl-Asp-Glu-Val-Asp-7-amido-4-trifluoromethylcoumarin cleavage activity and in situ poly(ADP-ribose) polymerase cleavage. Caspase activation coincided with the induction of apoptosis and capsid cleavage to the 40 kDa fragment. An in vitro cleavage assay, using recombinant human caspases and in vitro-derived FCV capsid protein, revealed that caspase-2, and to a lesser extent caspase-6, cleaved the capsid protein to generate a 40 kDa fragment. Taken together, these results suggest that FCV triggers apoptosis within infected cells and that caspase-induced capsid cleavage occurs concomitantly with apoptosis. The possible role of capsid cleavage in the pathogenesis of FCV infection is discussed.

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Keywords

40 kDa fragment
 
acute upper respiratory tract disease
 
capsid cleavage
 
capsid protein
 
Caspase activation
 
caspase inhibitors
 
caspase-2
 
caspase-induced capsid cleavage
 
FCV capsid protein
 
FCV infection
 
FCV triggers apoptosis
 
lesser extent caspase-6
 
mature 62 kDa capsid protein
 
N-acetyl-Asp-Glu-Val-Asp-7-amido-4-trifluoromethylcoumarin cleavage activity
 
N-terminal 124 amino acids
 
possible role
 
pro-form processing
 
recombinant human caspases
 
vitro cleavage assay
 
vitro-derived FCV capsid protein