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: 3.18). 06/2003; 84(Pt 5):1237-44.
Source: PubMed


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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    • "The activation of caspase 3, together with additional components of the mitochondrial pathway of apoptosis activation , was found also in FCV infected cells (Natoni et al., 2006). Furthermore, an in vitro cleavage assay revealed that caspase-2, as well as caspase-6, cleaved the FCV capsid protein to generate a 40 -kDa fragment suggesting a possible role of capsid cleavage in the life cycle of FCV infection (Al-Molawi et al., 2003). It will be important to verify whether caspase or other cell proteasemediated cleavages are required for replication of the virus, or merely a by-product of apoptosis or necrotic cell death. "
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    • "It has been reported previously that non-caliciviral proteases are capable of processing LC-VP1 as maturation of VP1 and VLP production was observed when LC-VP1 was expressed in CRFK cells and other cell lines when co-infected with Vaccinia virus [44], [45]. It is also possible that the production of an apparent mature capsid cleavage product is the result of cleavage by cellular caspases, induced as the result of multiple transfections, and previously known to process the FCV capsid protein [46]. In addition, we cannot formally exclude the possibility that very low levels of NS6-7 were present due to small amount of genomic RNA not removed during RNase H treatment. "
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