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Detection of feline coronavirus mutations in tissues in cats

Sangl L, Matiasek K, Felten S, et al. Detection of feline coronavirus mutations in paraffin-embedded tissues in cats with feline infectious peritonitis and controls. J Feline Med Surg. 2018 Mar 1:1098612X18762883. doi: 10.1177/1098612X18762883.

Feline infectious peritonitis (FIP) is caused by one of two feline coronavirus (FCoV) biotypes, a less frequently appearing FIP virus (FIPV) creating a lethal immune response in cats. Feline enteric coronavirus (FECV) is a benign yet much more common biotype form of FCoV, which frequent mutations of this form of RNA virus can lead to development of FIPV within infected cats.

Research in recent years has focused closely on two mutations in nucleotide 23531 and nucleotide 23537 in the spike (S) gene. These mutations result in the substitution of methionine to leucine codon at position 1058 (M1058L) and a substitution of a serine to alanine codon at position 1060 (S1060A) of the spike protein, and have been considered responsible for the biotype switch and enhanced macrophage tropism. Other mutations are also hypothesized to play a role, such as 3c, 7a, 7b gene, or the furin cleavage site in the region between receptor-binding (S1) and fusion (S2) domains of the spike gene, enhancing virus uptake by macrophages. The aim of this study was to determine the presence of mutated virus in tissue samples of cats with and without FIP.

This study included 64 cats in total, 34 diagnosed with FIP and 30 classified as control animals. The cats diagnosed with FIP were included based on macroscopic along with histological changes consistent with FIP and a positive IHC staining of tissue samples. RT-qPCR testing was applied to the tissue samples to discriminate the FCoV genotype.

Because FIP is typically fatal once a diagnosis is confirmed, the authors noted that specificity of a diagnostic test is more important than sensitivity due to the fact that a false (positive) diagnosis might lead to euthanasia of a cat. The specificity of the genotype-discriminating RT-qRCP was 100% and sensitivity was 70.6%. 23 of 34 cats with FIP tested positive for FIP. Of the positive samples, 23 demonstrated the amino acid substitution M1058L in the spike protein and none of the substitution S1060A.

The results indicate that since none of the control animals showed FCoV amino acid substitutions previously demonstrated in cats with FIP, the authors conclude that the substitution M1058L correlates with the presence of FIP. This substitution in the spike protein appears then to be strongly associated with the genotype switch from FECV to FIPV. (VT)

See also:

Longstaff L, Porter E, Crossley VJ, et al. Feline coronavirus quantitative reverse transcriptase polymerase chain reaction on effusion samples in cats with and without feline infectious peritonitis. J Feline Med Surg. 2017 Feb; 19(2):240-245.