Loss of FCoV-23 spike domain 0 enhanced viral entry kinetics by up to 3.9-fold in feline cells and markedly increased fusogenicity compared to the full-length spike protein.
The structural and functional characterization of FCoV-23 spike isoforms reveals mechanisms of enhanced fusogenicity and receptor tropism, paving the way for targeted vaccines and therapeutics.
. FCoV-23 is a recently emerged, highly pathogenic recombinant coronavirus responsible for a widespread outbreak of feline infectious peritonitis. Here we report cryogenic electron microscopy structures of two FCoV-23 spike isoforms that correspond to the in-host loss of domain 0 observed in clinical samples. The loss of domain 0 markedly enhances the fusogenicity and kinetics of entry into cells and possibly enables biotype switching and lethality. We show that FCoV-23 can use several aminopeptidase N orthologues as receptors and reveal the molecular determinants of receptor species tropism, including a glycan that modulates human receptor engagement. We define antigenic relationships among alphacoronaviruses that infect humans and other mammalian species and identify a cross-reactive alphacoronavirus monoclonal antibody that inhibits FCoV-23 entry. Our results pave the way for the development of vaccines and therapeutics that target this highly pathogenic virus.
Tortorici et al. (Wed,) conducted a other in Feline infectious peritonitis. FCoV-23 S-short (loss of domain 0) vs. FCoV-23 S-long was evaluated on Viral entry kinetics and fusogenicity. Loss of FCoV-23 spike domain 0 enhanced viral entry kinetics by up to 3.9-fold in feline cells and markedly increased fusogenicity compared to the full-length spike protein.
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