Feline coronavirus: mechanisms of entry into the host cell
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Jaimes Olaya, Javier Andres
Feline coronavirus (FCoV) is an etiological agent causing either a sub-clinical disease (feline enteric coronavirus – FECV) or a fatal systemic disease (feline infectious peritonitis virus –FIPV). Two FCoV serotypes have been described, the serotype I virus that is clinically prevalent, and the serotype II virus, which is clinically less common but grows easily in cell culture. The FCoV spike (S) protein is considered the viral regulator for entry into the cell. This regulation is carried out by the major functions of S; receptor binding and virus-cell membrane fusion. However, little is known about the mechanisms used by FCoV to enter into the cell. This present work aims to better understand those mechanisms. First, the FCoV S proteins from FIPV I Black, FECV II 1683 and FIPV II 1146 strains were modeled and studied to determine their structural characteristics. Differences between serotype I and II were observed in the S models, specifically at the S1/S2 and S2’ cleavage sites, suggesting different mechanisms for S activation between serotypes. To better study this, functional experiments were performed to evaluate the role of cellular proteases in FCoV S activation. Cathepsin B was found to activate all the studied FCoV S proteins, but at different sites depending on the serotype, demonstrating the important role of this protease in FCoV S function. Finally, the role of calcium in FCoV entry was also studied. FCoV S was shown to behave in a calcium dependent manner and depletion of this ion resulted in a dramatic decrease in FCoV replication. Overall, the results obtained in this research showed that serotype I and II FCoV are biologically distinct, with cathepsin B able to act as a common activator for FCoV S and its fusion function being calcium dependent.
Feline infectious peritonitis; Molecular biology; Animal diseases; Virology; Entry mechanisms; Feline coronavirus; Coronavirus; Spike protein
Whittaker, Gary R.
Casey, James Wilton; Van de Walle, Gerlinde
Doctor of Philosophy
dissertation or thesis