Limitations of using feline coronavirus spike protein gene mutations to diagnose feline infectious peritonitis

Barker, Emily N.; Stranieri, Angelica; Helps, Chris R.; Porter, Emily L.; Davidson, Andrew D.; Day, Michael J.; Knowles, Toby; Kipar, Anja; Tasker, Séverine

It has been previously proposed that the M1058L or S1060A substitutions could affect the fusogenic activity and cell receptor specificity of the FCoV S protein [18, 20] , permitting entry into macrophages and monocytes. It is further proposed that additional FCoV mutations, along with changes within the host's immunological response, are required to permit the seemingly uncontrolled replication seen during the development of FIP. These hypotheses are supported by the present study: firstly, the finding that the majority of FCoV detected in tissue samples from both cats with FIP and cats without FIP have M1058L or S1060A substitutions in the FCoV S protein; and secondly, as also described in a previous study of naturally infected cats [10] , the finding that FCoV RNA was detected in a far greater proportion of tissue samples from cats with FIP (90.4%) than tissue samples from cats without FIP (7.8%), and, in those samples that were RT-qPCR positive, significantly higher FCoV relative copy numbers were found in the FIP samples (median 8.3 × 10 3 vs. 25; U = 2161.5, p ≤ 0.001). Other viral genomic mutations have also been associated with FIP, but were not evaluated as part of this study. For example, mutations in the S protein gene encoding amino acid differences in the furin cleavage motif [37] and the heptad HR1 region of the S2 subunit [38] have been correlated with disease. Truncations of the accessory protein 3c gene have also been associated with loss of ability to replicate within enterocytes and, as such, have only been reported in FIP-associated FCoVs [35] . However, characterisation of these viral genomic mutations was not within the aims of this study, and use of these viral genomic mutations in the diagnosis of FIP has, so far, not been suggested.