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Spike Protein Mutation Linked Only to Spread of Feline Coronavirus not to FIP Conversion

Porter E, Tasker S, Day MJ, et al. Amino acid changes in the spike protein of feline coronavirus correlate with systemic spread of virus from the intestine and not with feline infectious peritonitis.  Veterinary Research 2014, 45: 49-59.

Feline infectious peritonitis (FIP) still has no cure, but a great deal has been learned about this disease in the past few years.  Infection with feline enteric coronavirus (FECV) is quite common, and it has been postulated and reconfirmed that at least 3 (i.e., ORF 3c accessory gene, spike (S) protein gene, and ORF 7b accessory gene) mutations in FECV within a single host cat lead to conversion to FIP.  This conversion is commonly referred to as the ‘internal mutation theory’.  Conversion to FIP initially involves switching from infection localized in the gastrointestinal tract to spreading to the rest of the body by acquiring the ability to infect macrophages or monocytes.  Macrophages are a type of white blood cell found in tissue that can engulf and digest cellular debris, foreign substances, microbes, and cancer cells and they help regulate immune system response.   Monocytes are macrophages found in the blood.

Intense interest has recently been sparked due to mutations identified in the spike (S) protein gene that are thought to confer the initial switch from only infecting intestinal cells to infecting macrophages1,2.   This is a reasonable thought since the spike protein fusion peptide is a critical element in the fusion of viral and host cell during virus entry3Specifically, Chang et al. (2012)1 and coworkers identified a specific genetic mutation that results in an amino acid change from methionine to leucine at position 1058 of the spike protein gene, and suggested this change is associated with FECV-to-FIP conversion.

Dr. Stuart Siddell’s at University of Bristol, UK and co-investigators examined 86 tissue and 26 fecal samples, collected post-mortem from cats diagnosed with or without FIP, using RNA extraction and quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) to detect feline coronavirus (FCoV) RNA.  In cats with FIP, 95% of tissue and 81% of fecal samples were PCR-positive.  In cats without FIP, 22% of tissue and 60% of fecal samples were PCR-positive.  Furthermore, samples that were positive for FCoV qRT-PCR had a 153 base-pair DNA fragment encompassing position 1058 in the spike protein sequenced using a pyrosequencing method.  The methionine codon at position 1058 in the spike protein, thought to be consistent with shedding the intestinal form (FECV) was found in 77% of fecal samples of cats with FIP and 100% of fecal samples of cats without FIP.  Surprisingly, the leucine codon at position 1058 in the spike protein, previously postulated to confer FECV-to-FIP conversion, was found in 91% of tissue samples from cats with FIP and 89% of cats without FIP.  Nine percent of FIP tissue samples had a methionine codon at position 1058.  This surprising result suggests that the methionine to leucine substitution confers spread of the coronavirus from the intestine, but it does not necessarily cause FIP. [GO]

See also:
1 Chang HW, Egberink HF, Halpin R, et al.  Spike protein fusion peptide and feline coronavirus virulence.  Emerg Infect Dis 2012, 18:1089-1095.

2 Licitra BN, Millet JK, Regan AD, et al. Mutation in spike protein cleavage site and pathogenesis of feline coronavirus.  Emerg Infect Dis 2013, 19:1066-1073. (Free article)

3 Bosch BJ, van der Zee R, de Haan CA, et al. The coronavirus spike protein is a class I virus fusion protein: structural and functional characterization of the fusion core complex.  J Virol 2003, 77:8801-8811.