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

Abstract

Case series summary This case series describes three shelter-housed cats concurrently diagnosed with feline infectious peritonitis (FIP). The cats were from a cohort of seven surrendered from the site of a house fire. The three cats presented with mild upper respiratory signs. Within 10 days they clinically declined: progressive signs included pyrexia, icterus, lethargy, anorexia and cavitary effusions. Necropsy followed by histopathology and immunohistochemistry confirmed a diagnosis of FIP in all three. Molecular analysis of the causative feline coronavirus (FCoV) revealed varied amino acid alterations in the spike gene both between cats and between sample types in individual cats. A fourth cat from the cohort remained healthy in the shelter but succumbed to FIP 6 weeks post-adoption. Relevance and novel information This case series places FCoV genetic sequences in the context of clinical signs in a small shelter outbreak. Each of the three cats concurrently developed a slightly different clinical presentation. PCR amplification and genetic sequencing revealed that two cats shared an S1/S2 cleavage site mutation (R790S) previously described to be associated with the development of FIP; one of the cats had an additional S1/S2 cleavage site mutation (R793S). The third cat had a single, identical S1/S2 point mutation (R790G) unique from the other two cats; the R790G mutation has not been previously reported. This case series provides interesting data on point mutations associated with the development of FIP and provides support for a ‘circulating virulent–avirulent theory’ of FIP pathogenesis in a small shelter outbreak.

Acute phase proteins in cats: Diagnostic and prognostic role, future directions, and analytical challenges

“…Remission is a source of concern because of the possibility of relapse. Relapse poses a risk for other cats sharing the same environment because infected cats can shed the virus 38,39 . APPs also play a role in the prognosis of FIP in cats treated with antivirals.…”

Natural selection differences detected in key protein domains between non-pathogenic and pathogenic Feline Coronavirus phenotypes

“…The FCoV-1 Spike S1/S2 furin cleavage site (FCS) is characterized by poly-basic residues S - R - R - S/ A - R - R - S (serine (S), arginine (R), alanine (A)), commonly labeled as P6 - P5 - P4 - P3 - P2 - P1 | P1’, with cleavage occurring between P1 and P1’ (Licitra et al, 2014; Thomas, 2002). Mutations differentiating FECV from FIPV sequences have been identified in this FCS (André et al, 2019; Healey et al, 2022; Licitra et al, 2013, 2014; Millet & Whittaker, 2015; Ouyang et al, 2022). A key feature of class l virus fusion proteins is the proximity of the heptad repeat regions 1 and 2 (HR-1 and HR-2, respectively) to the fusion domain (FD) (Bosch et al, 2003).…”

“…The main hypothesis for how FIP develops from an FCoV infection is the “internal mutation” hypothesis, which states that the emergence of virulent, de novo mutations from within FECV genomes during infection gives rise to FIPV (H. W. Chang et al, 2011; H.-W. Chang et al, 2010; Herrewegh et al, 1995; Pedersen, 2009; Pedersen et al, 2012; Poland et al, 1996; Stoddart & Scott, 1989; Vennema et al, 1998). The “circulating virulent-avirulent FCoV” hypothesis is less empirically supported, and posits that non-pathogenic and pathogenic strains of FCoV constantly circulate throughout feline populations and FIP results from transmission of the pathogenic biotype (Brown et al, 2009; Healey et al, 2022).…”

Clinical and Molecular Relationships between COVID-19 and Feline Infectious Peritonitis (FIP)

“…In these situations, the stress of overcrowding and high levels of virus in the environment may favor the transition of FECV into FIPV. There is evidence some strains of FCoV may be more predisposed to this transition than others [ 18 , 19 ].…”