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Spike protein fusion peptide and feline coronavirus virulence.

Chang HW, Egberink HF, Halpin R, Spiro DJ, Rottier PJ - Emerging Infect. Dis. (2012)

Bottom Line: 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.Evidence indicates that FIPV originates from FECV by mutation, but consistent distinguishing differences have not been established.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.

View Article: PubMed Central - PubMed

Affiliation: Virology Division, Department of Infectious Diseases and Immunology, Veterinary Faculty, Utrecht University, Utrecht, the Netherlands.

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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Related in: MedlinePlus

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.
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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.

Mentions: To further investigate the single most prominent region of difference between FECVs and FIPVs, we established an RT-nPCR method to amplify and analyze the genomic region covering nucleotides 23442–24040 for the first PCR run and nucleotides 23451–23593 for the second run, which includes deviant position 23531. Altogether, 183 FECV and 118 FIPV RNAs isolated from different cats were sequenced in this specific region. Results for the 11 entirely sequenced FECVs and FIPVs are shown in Figure 2. The A at nucleotide 23531 was 100% conserved in all 183 FECVs in our collection. Of the 118 FIPVs, 96 (81.4%) had a T and 12 (10.2%) a C at this position; in both cases, this changes the methionine occurring at position 1058 in the FECV S protein into a leucine in FIPV (i.e., mutation M1058L).


Spike protein fusion peptide and feline coronavirus virulence.

Chang HW, Egberink HF, Halpin R, Spiro DJ, Rottier PJ - Emerging Infect. Dis. (2012)

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.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3376813&req=5

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.
Mentions: To further investigate the single most prominent region of difference between FECVs and FIPVs, we established an RT-nPCR method to amplify and analyze the genomic region covering nucleotides 23442–24040 for the first PCR run and nucleotides 23451–23593 for the second run, which includes deviant position 23531. Altogether, 183 FECV and 118 FIPV RNAs isolated from different cats were sequenced in this specific region. Results for the 11 entirely sequenced FECVs and FIPVs are shown in Figure 2. The A at nucleotide 23531 was 100% conserved in all 183 FECVs in our collection. Of the 118 FIPVs, 96 (81.4%) had a T and 12 (10.2%) a C at this position; in both cases, this changes the methionine occurring at position 1058 in the FECV S protein into a leucine in FIPV (i.e., mutation M1058L).

Bottom Line: 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.Evidence indicates that FIPV originates from FECV by mutation, but consistent distinguishing differences have not been established.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.

View Article: PubMed Central - PubMed

Affiliation: Virology Division, Department of Infectious Diseases and Immunology, Veterinary Faculty, Utrecht University, Utrecht, the Netherlands.

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.

Show MeSH
Related in: MedlinePlus