Caspase-mediated cleavage of the feline calicivirus capsid protein.
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.
Al-Molawi
Naema
N
School of Biomedical and Life Sciences, University of Surrey, Guildford, Surrey GU2 7XH, UK.
Beardmore
Victoria A
VA
School of Biomedical and Life Sciences, University of Surrey, Guildford, Surrey GU2 7XH, UK.
Carter
Michael J
MJ
School of Biomedical and Life Sciences, University of Surrey, Guildford, Surrey GU2 7XH, UK.
Kass
George E N
GEN
School of Biomedical and Life Sciences, University of Surrey, Guildford, Surrey GU2 7XH, UK.
Roberts
Lisa O
LO
School of Biomedical and Life Sciences, University of Surrey, Guildford, Surrey GU2 7XH, UK.
D000818:Animals; D017209:Apoptosis; D017927:Calicivirus, Feline / Q000472:pathogenicity*; D036022:Capsid Proteins / Q000378:metabolism*; D061945:Caspase Inhibitors; D020169:Caspases / Q000235:genetics / Q000378:metabolism*; D002415:Cats; D002460:Cell Line; D004789:Enzyme Activation; D006801:Humans; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
D036022:Capsid Proteins; D061945:Caspase Inhibitors; D011994:Recombinant Proteins; D020169:Caspases