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Outbreak of feline infectious peritonitis (FIP) in shelter-housed cats: molecular analysis of the feline coronavirus S1/S2 cleavage site consistent with a ‘circulating virulent–avirulent theory’ of FIP pathogenesis

Healey EA, Andre NM, Miller AD, Whittaker GR, Berliner EA. Outbreak of feline infectious peritonitis (FIP) in shelter-housed cats: molecular analysis of the feline coronavirus S1/S2 cleavage site consistent with a ‘circulating virulent–avirulent theory’ of FIP pathogenesis. Journal of Feline Medicine and Surgery Open Reports. 2022;8(1). doi:10.1177/20551169221074226

Feline infectious peritonitis (FIP) is a fatal disease in cats caused by the mutation of the common virus feline enteric coronavirus (FECV). Literature continues to evolve on this topic, including the 2022 AAFP/EveryCat Diagnostic Guidelines that readers are invited to review for additional background information.

Traditionally, this condition has been considered a disease of ‘individuals’ and outbreaks have been considered exceedingly rare. Two theories exist to account for this:
1. Internal mutation theory: FECV mutates within the infected host to FIPV independently.
2. Horizontal transmission: Cats may at times transmit FIPV directly, which is rare.

This recent case series proposed a variation of the internal mutation theory called the ‘circulating virulent-avirulent theory’ as the cause of 3 shelter-housed cats simultaneously developing FIP. In this theory, specific strains of FECV circulate in a population and the most susceptible cats develop FIP via internal mutation.

Background information on this case series:
• Seven sexually intact cats were observed and retrieved several days after a house fire around the remains of the home.
• Age estimates of the cats ranged from 6-18 months.
• All seven cats were taken to a private animal shelter (less than 1500 admissions per year), placed in individual housing, and received intake care overseen by a staff veterinarian.
• Three cats presented with varying clinical signs of upper respiratory disease, and within 10 days developed clinical signs suggestive of FIP.
• These cats all became febrile with some degree of ultrasound evidence of effusion (peritoneal, pleural, or pericardial). Two of the cats had varying bloodwork abnormalities (the third did not have any bloodwork performed).
• Due to rapid decline in health status, all three cats were euthanized and submitted for necropsy, tissue sampling, and molecular analysis.
• The remaining four cats appeared to be in excellent health after the diagnosis of FIP was confirmed, but 6 weeks later, one of these cats became acutely ill, reportedly had symptoms consistent with FIP, and was euthanized by a primary care veterinarian. No necropsy or diagnostic testing was reported in this patient.
• Two of the remaining three cats were alive 2 years later, with the third lost to follow-up.

The results of the diagnostic and molecular testing in the three cats were the following:
• Immunohistochemistry (IHC) performed on tissues on each cat confirmed the diagnosis of FIP.
• Viral RNA was PCR amplified and sequenced in each individual animal.
• All three cats were infected with viruses containing different spike protein cleavage site (S1/S2) sequences.
• In two of these cats, a similar sequence of mutations occurred.
• The third cat showed a distinct but consistent mutation in both tissue and effusion which had not been previously recognized.

How are these results interpreted?
This report adds more published data to an already complex disease process. These three simultaneous cases of FIP are most consistent with the ‘circulating virulent-avirulent theory’: each cat shared a distinct but common feline coronavirus that developed key mutations internally leading to the fatal outcome. Stressors, including the house fire, capture, and shelter admission, likely drove the development of FIP in an already primed circulating coronavirus.

As the affected cats had varying molecular sequences, the horizontal transmission theory does not hold.   ~BJP


See Also:

André NM, Miller AD, Whittaker GR. Feline infectious peritonitis virus-associated rhinitis in a cat. JFMS Open Rep. 2020 Jun 23;6(1):2055116920930582. doi: 10.1177/2055116920930582. PMCID: PMC7313338.

Emmler L, Felten S, Matiasek K, Balzer HJ, Pantchev N, Leutenegger C, Hartmann K. Feline coronavirus with and without spike gene mutations detected by real-time RT-PCRs in cats with feline infectious peritonitis. J Feline Med Surg. 2020 Aug;22(8):791-799. doi: 10.1177/1098612X19886671. Epub 2019 Nov 15. PMID: 31729897; PMCID: PMC7206566.