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. 2012 Jul;18(7):1089-95.
doi: 10.3201/eid1807.120143.

Spike protein fusion peptide and feline coronavirus virulence

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Spike protein fusion peptide and feline coronavirus virulence

Hui-Wen Chang et al. Emerg Infect Dis. 2012 Jul.

Abstract

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 identified 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.

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Figures

Figure 1
Figure 1
Comparison of full genomes of 11 lethal feline infectious peritonitis viruses (FIPVs) with full genomes of 11 nonvirulent feline enteric coronaviruses (FECVs). Nucleotide (nt) positions are shown on the x-axis; y-axis indicates number of FIPV genomes for which the identity at the nt position differed from identity at same position in all FECV genomes. FIPV strain C1Je (GenBank accession no. DQ848678) was used as the reference for nt numbering. *Highest difference score: 9 FIPVs had identities at nt position 23531 that differed from those at the same position in all FECVs. 1a, gene 1a; 1b, gene 1b; S, spike protein gene; 3abc, gene cluster 3abc; E, envelope protein gene; M, membrane protein gene; N, nucleocapsid protein gene; 7ab, gene cluster 7ab.
Figure 2
Figure 2
Alignment of partial nucleotide sequences and translated amino acid sequences in the spike protein of 11 strains each of 2 feline coronavirus pathotypes: FIPVs (lethal) and FECVs (nonvirulent). The viruses were sequenced in a study to distinguish virulent from nonvirulent feline coronaviruses (see Table 1). FIPV strain C1Je (GenBank accession no. DQ848678) was used as the reference for numbering. Sequence positions are shown along the top; virus strains are shown on the right. Specific differences between the pathotypes are boxed. FIPVs, feline infectious peritonitis viruses; FECVs, feline enteric coronaviruses.
Figure 3
Figure 3
Phylogenetic tree based on partial amino acid sequences (aa 1056–1069) of the spike proteins of 118 feline infectious peritonitis viruses (FIPVs) and 183 feline enteric coronaviruses (FECVs) obtained by using reverse transcription nested PCR and sequencing of the distinguishing genomic region. A circular rooted neighbor-joining tree was constructed by using the bootstrap method and applying 1,000 replicates. Black dots indicate FIPVs. Clade A comprises FIPVs containing the M1058L mutation; clade B comprises FIPVs containing the S1060A mutation.

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