Mutations of 3c and spike protein genes correlate with the occurrence of feline infectious peritonitis

Abstract

The genes encoding accessory proteins 3a, 3b, 3c, 7a and 7b, the S2 domain of the spike (S) protein gene and the membrane (M) protein gene of feline infectious peritonitis virus (FIPV) and feline enteric coronavirus (FECV) samples were amplified, cloned and sequenced. For this faeces and/or ascites samples from 19 cats suffering from feline infectious peritonitis (FIP) as well as from 20 FECV-infected healthy cats were used. Sequence comparisons revealed that 3c genes of animals with FIP were heavily affected by nucleotide deletions and point mutations compared to animals infected with FECV; these alterations resulted either in early termination or destruction of the translation initiation codon. Two ascites-derived samples of cats with FIP which displayed no alterations of ORF3c harboured mutations in the S2 domain of the S protein gene which resulted in amino acid exchanges or deletions. Moreover, changes in 3c were often accompanied by mutations in S2. In contrast, in samples obtained from faeces of healthy cats, the ORF3c was never affected by such mutations. Similarly ORF3c from faecal samples of the cats with FIP was mostly intact and showed only in a few cases the same mutations found in the respective ascites samples. The genes encoding 3a, 3b, 7a and 7b displayed no mutations linked to the feline coronavirus (FCoV) biotype. The M protein gene was found to be conserved between FECV and FIPV samples. Our findings suggest that mutations of 3c and spike protein genes correlate with the occurrence of FIP.

Coronavirus Spike Protein and Tropism Changes

“…Mutations in other parts of the S 2 subunit than those affecting the proteolytic cleavage sites may also influence the tropism of different CoVs. Several studies report a correlation between mutations in the HR1 region of FCoVs and the conversion of FECV into FIPV (Bank-Wolf et al, 2014;Desmarets et al, 2016;Lewis et al, 2015). Such a correlation appeared even more convincing for mutations found in the recently identified FP2 (Chang et al, 2012;Ou et al, 2016).…”

Experimental feline enteric coronavirus infection reveals an aberrant infection pattern and shedding of mutants with impaired infectivity in enterocyte cultures

“…In contrast to the S1 domain, the S2 domain of the spike was less affected by mutations, as only one amino acid change had occurred in cat 2 and cat 3. One of these mutations (T1107I in cat 2) occurred in the heptad repeat 1 (HR1), a region that was recently shown to be affected by mutations in many FIP cats 24,25 . If one or more of these mutations in the spike protein can be linked to the reduced in vitro enterocyte tropism requires further investigation.…”

“…4 GenBank accession numbers KU215427 (with S1 deletion) and KU215428 (without S1 deletion). 5,6,7,9,12,13,14,15,16,17,18,20,21,22,23,28 100%, 8 97.8%, 10 12.1%, 11 18.6%, 19 79.3%, 24 24.3%, 25 actual enterotropic strains, but rather variant forms with a yet unclear cell tropism. Although no FIPV-associated mutations 5,9,31,32 were found and none of the cats developed FIP, this continuous selection pressure on the virus may successively induce FIPV-specific mutations/glycosylation and/or result in mutations/deletions in no longer required (parts of) proteins, explaining the myriad of genetic changes found in FIP affected cats.…”

Expression profiles of immune mediators in feline Coronavirus-infected cells and clinical samples of feline Coronavirus-positive cats

“…Currently, there are no specific markers to distinguish the two biotypes, thus making the diagnosis of feline infectious peritonitis (FIP) difficult. Although several studies have reported several point mutations in the S gene that are associated with occurrence of FIPV, it remains unclear whether the mutations contributed solely to the development of FIP [5][6][7]. Therefore, antemortem confirmation of FIP remains a challenging task in clinical research of FIP.…”