Epidemiology and Comparative Analyses of the S Gene on Feline Coronavirus in Central China

Abstract

Feline coronavirus (FCoV) infections present as one of two forms: a mild or symptom-less enteric infection (FEC) and a fatal systemic disease termed feline infectious peritonitis (FIP). The lack of epidemiology of FCoV in central China and the reason why different symptoms are caused by viruses of the same serotype have motivated this investigation. Clinical data of 81 suspected FIP cases, 116 diarrhea cases and 174 healthy cases were collected from veterinary hospitals using body cavity effusion or fecal samples. Risk factors, sequence comparison and phylogenetic studies were performed. The results indicated that FIPV was distinguished from FECV in the average hydrophobicity of amino acids among the cleavage sites of furin, as well as the mutation sites 23,531 and 23,537. FIPV included a higher minimal R-X-X-R recognition motif of furin (41.94%) than did FECV (9.1%). The serotype of FCoV was insignificantly correlated with FIP, and the clade 1 and clade 2 strains that appeared were unique to central China. Thus, it is hypothesized that this, along with the latent variables of an antigenic epitope at positions 1058 and 1060, as well as mutations at the S1/S2 sites, are important factors affecting FCoV transmission and pathogenicity.

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

“…Out of the 46 sites either manually identified or reported in an earlier selection analysis (ESA) to differentiate FIPV from FECV sequences within RFPs associated with either FIPV or FECV positive selection, four were subject to positive selection associated with FIPV and two exhibited differences in selective regimes between FIPV and FECV sequences. The site most consistently reported in the literature differentiating FIPV from FECV and subject to positive selection was site 1058 (Bank-Wolf et al, 2014; Barker et al, 2017; H.-W. Chang et al, 2012; Decaro et al, 2021; Lewis et al, 2015; Ouyang et al, 2022; Xia et al, 2020) and our analyses suggest that this site also has a history of convergent evolution ( Fig. 3 ).…”

“…Perhaps, FIPV is using a furin cleavage-independent means of cellular entry, and may be using a co-receptor such as (fDC-SIGN or sialic acid). Importantly, it is encouraging that our hypothesis that the P4 site within the S1/S2 Spike-1 FCS may be putatively phenotype-altering is supported by newly collected data (Ouyang et al, 2022). Due to the conservative amino acid nature of this site in nonpathogenic sequences compared to the amino acid diversity observed in pathogenic sequences, this site may provide a useful diagnostic tool to identify FIPV sequences.…”

“…In instances where BUSTED-PH associated selection with the FIPV phenotype (Spike-1: RFPs 1, 5, 11, Spike-2: RFP 8) we identified 11 sites subject to selection not reported in the literature; 10 in Spike-1 and one in Spike-2 (Table 2), with the greatest concentration in the 0-domain of Spike-1 (Fig. 1A; Chang et al, 2012;Decaro et al, 2021;Lewis et al, 2015;Ouyang et al, 2022;Xia et al, 2020) and our analyses suggest that this site also has a history of convergent evolution (Fig. 3).…”

“…2 ). Recent work from Ouyang et al, 2022 demonstrated that amino acid composition at the P4 site was highly diversified in FIPV sequences, while high amino acid conservation was observed in non-FIP sequences. Within Betacoronaviruses , such as Mouse Hepatitis Virus (MHV), a highly conserved P4 site (arginine) is also apparent (Stout et al, 2021).…”

“…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).…”