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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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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.
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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.

Mentions: Our results showed that differences were scattered along the entire genome (Figure 1). At 2,963 (10%) of the 29,277 genome positions, the nucleotide identity in at least 1 of the 11 FIPVs did not occur in any of the 11 FECVs. Of these 2,963 positions, 1,187 occurred in gene 1ab, 1,246 in the S gene, 248 in gene cluster 3abc, 22 in the envelope protein gene, 42 in the membrane protein gene, 113 in the nucleocapsid protein gene, and 106 in gene cluster 7ab, showing the disproportionally large genetic variation in the S gene. The frequency with which differences occurred at different nucleotide positions across the genome showed the following distribution: a difference was detected 1× at 1,914 positions, 2× at 945 positions, 3× at 87 positions, 4× at 15 positions, and 5× at 1 position. At 1 position (23531), the nucleotide identity in 9 of the FIPVs was not found in any of the FECVs. No position(s) uniquely distinguished the 2 FCoV pathotypes.


Spike protein fusion peptide and feline coronavirus virulence.

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

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.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3376813&req=5

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.
Mentions: Our results showed that differences were scattered along the entire genome (Figure 1). At 2,963 (10%) of the 29,277 genome positions, the nucleotide identity in at least 1 of the 11 FIPVs did not occur in any of the 11 FECVs. Of these 2,963 positions, 1,187 occurred in gene 1ab, 1,246 in the S gene, 248 in gene cluster 3abc, 22 in the envelope protein gene, 42 in the membrane protein gene, 113 in the nucleocapsid protein gene, and 106 in gene cluster 7ab, showing the disproportionally large genetic variation in the S gene. The frequency with which differences occurred at different nucleotide positions across the genome showed the following distribution: a difference was detected 1× at 1,914 positions, 2× at 945 positions, 3× at 87 positions, 4× at 15 positions, and 5× at 1 position. At 1 position (23531), the nucleotide identity in 9 of the FIPVs was not found in any of the FECVs. No position(s) uniquely distinguished the 2 FCoV pathotypes.

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