Distinct mutation in the feline coronavirus spike protein cleavage activation site in a cat with feline infectious peritonitis-associated meningoencephalomyelitis

André, Nicole M; Cossic, Brieuc; Davies, Emma; Miller, Andrew D; Whittaker, Gary R

Here we report clinicopathologic findings and molecular analysis of a cat with progressive neurologic clinical signs associated with FIP. The cat initially presented to the referring veterinarian with respiratory signs and fever, and with abnormal liver enzyme function and anemia. At this time FIP was not suspected. These initial signs resolved but were replaced by progressing neurologic signs, which led ultimately to euthanasia and submission to the study for evaluation of FCoV involvement. Upon euthanasia, FCoV was found in various tissues in the cat, including the CNS. However, histologic examination revealed FCoV-associated pathology only within the CNS, where there was meningoencephalomyelitis, ependymitis, choroid plexitis and vasculitis. Histo logical lesions were compatible with a recent report describing meningoencephalitis in four cats with FIP. 18 Molecular analysis of the viral spike protein within the tissues identified a specific, functionally relevant amino acid change (R793M), which was only identified in tissues associated with the CNS (ie, brain and spinal cord). The R793M mutation in the spike protein S1/S2 cleavage-activation site is a major chemical change from a basic to a hydrophobic residue, and is consistent with an elimination of furin-mediated proteolytic processing of the S protein, as seen by Licitra et al, 17 and a proposed change in the activation properties and entry pathway of the virus. It is interesting to note that the R793M mutation was not present in other tissues tested in this cat at the time of necropsy but was found in our previous study (cat ID #08-153990), 17 where samples were of neural origin. While biological confirmation is not available, we consider that the other changes found in the viral spike protein from central nervous tissue of this cat (A770V and T786A) are not related to changes in the activation properties and entry pathway of the virus, as they are not in defined functional regions of the spike protein and are not markedly different in their chemistry. Interestingly, all samples tested from this cat contained a distinct leucine residue at position 791 (the P3 position of the furin cleavage site, typically serine or alanine as defined in Licitra et al). 17 The relevance of this is currently unclear. Overall, our results provide evidence that mutation of the viral spike protein is linked to FIP outcome, specifically in the S1/S2 cleavage-activation site (residues 789-794).