Niels C. Pedersen, DVM, PhD
The ubiquitous form of feline coronavirus is readily passed cat-to-cat by the fecal-oral route and is the cause of mild or unapparent enteritis. Like coronaviruses in general, feline enteric coronavirus (FECV) is undergoing constant mutation within its accessory and structural genes. Feline infectious peritonitis (FIP), which is a highly fatal systemic disease, appears to arise as an internal mutation during the course of FECV infection. The most common mutation reflecting the biotype switch from FECV to FIPV is in an accessory gene called 3c. Deleterious mutations in 3c tend to be found in diseased internal tissues, while viruses with intact 3c are found mainly in the feces. Some cats with FIP, especially random breeds, appear at firsthand to have intact 3c genes. However, minor variants with deleterious mutations in the 3c gene are observed in a proportion of such isolates. Studies are underway on FIP isolates that appear to have only intact 3c genes; such studies will require much more extensive sequencing (replicase/transcriptase genes as well as accessory and structural genes) and animal inoculation studies to determine alternative mutations that might be associated with the FIP biotype. However, evidence suggests that deleterious 3c gene mutations are the most important. All FIPV strains used for animal inoculation studies contain a mutated 3c gene, while all bona fide FECVs have intact 3c genes and cause primarily enteritis. 3c gene mutants, when they occur, tend to be unique to each FIP cat, indicating that they arise independently in each host and not from mutation in one cat with subsequent horizontal spread to others. Minor genetic variants often co-exist in both tissues and feces, although variants with intact 3c genes tend to be found in feces and variants with mutated 3c genes tend to be found in lesional tissues. When co-existing variants are inoculated into the same cat, one or the other, but not both will predominate. The high mutability of feline coronaviruses leads to minor genetic differences between cats in one closely contained geographic area, while significant genetic differences are seen between isolates from geographically disparate regions. Genetic drift across regions appears to be due to both intra- and inter-cat mutation and specific variant selection. The 3c gene of feline coronaviruses has a 30% genetic homology and identical hydrophilicity profile to the 3a gene and protein of the human SARS coronavirus. Extensive research into the function of the SARS coronavirus 3a gene and its protein may provide interesting insights into the function of the 3c gene and protein in FIP.