Spike Protein Fusion Peptide and Feline Coronavirus Virulence

Пептид слияния шипкового белка и вирулентность коронавирусов кошек
Hui‐Wen Chang, Peter J. M. Rottier, Rebecca Halpin, David Spiro, Herman Egberink
2012-06-08

Feline coronavirusFeline infectious peritonitis virusMacrophage tropismPathotype differentiationSpike protein fusion peptide
Coronaviruses are well known for their potential to change their host or tissue tropism, resulting in unpredictable new diseases and changes in pathogenicity; severe acute respiratory syndrome and feline coronaviruses, respectively, are the most recognized examples.Feline coronaviruses occur as 2 pathotypes: nonvirulent feline enteric coronaviruses (FECVs), which replicate in intestinal epithelium cells, and lethal feline infectious peritonitis viruses (FIPVs), which replicate in macrophages.Evidence indicates that FIPV originates from FECV by mutation, but consistent distinguishing differences have not been established.We sequenced the full genome of 11 viruses of each pathotype and then focused on the single most distinctive site by additionally sequencing hundreds of viruses in that region.As a result, we identifi ed 2 alternative amino acid differences in the putative fusion peptide of the spike protein that together distinguish FIPV from FECV in >95% of cases.By these and perhaps other mutations, the virus apparently acquires its macrophage tropism and spreads systemically.C oronaviruses (subfamily Coronavirinae, order Nido- virales) are enveloped, plus-strand RNA viruses that infect mammals and birds.They are quite common and cause infections in humans and a wide variety of animals; infection typically results in respiratory or enteric disease.Severe acute respiratory syndrome coronavirus (SARS-CoV), which emerged suddenly in 2002 and caused severe acute respiratory disease in humans, is the most notorious coronavirus.SARS-CoV spread rapidly around the globe, infecting thousands and killing ≈800 persons.The virus Spike Protein Fusion Peptide and Feline Coronavirus Virulence
1
Feline coronaviruses occur as nonvirulent enteric FECVs and lethal macrophage-tropic FIPVs with distinct tissue tropisms.
2
Full-genome sequencing of 11 viruses from each pathotype identified the spike protein’s putative fusion peptide as the most distinctive region.
3
The findings support the emergence of FIPV from FECV through mutation, while not establishing a completely consistent genetic distinction between pathotypes.
4
These mutations, potentially together with additional changes, may enable acquisition of macrophage tropism and systemic viral spread.
5
Two alternative amino acid differences in the putative spike fusion peptide distinguish FIPV from FECV in more than 95% of cases.

Feline coronaviruses, specifically nonvirulent feline enteric coronaviruses (FECVs) and lethal feline infectious peritonitis viruses (FIPVs)

The association of alternative amino acid differences in the spike-protein fusion peptide with macrophage tropism, systemic spread, and virulence/pathotype distinction

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2012-06-08
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Hui‐Wen Chang
Peter J. M. Rottier
Rebecca Halpin
David Spiro
Herman Egberink
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