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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

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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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.

Mentions: Assuming that the difference observed in 108 of the 118 sequenced FIPVs may be responsible for the virulent phenotype, the remaining 10 viruses should be expected to carry alternative differences. In search of those differences, we performed a phylogenetic analysis of the partial nucleotide sequences accumulated by the RT-nPCR procedure, but the results did not enable further differentiation (data not shown). When carrying out a phylogenetic analysis of the translated partial amino acid sequences, we observed a small but distinct second cluster B in addition to the major cluster A constituted by the FIPVs having leucine at position 1058 in their S protein (Figure 3). This smaller cluster, formed by 5 (4.2%) of the sequenced FIPVs, appeared to be characterized by the occurrence of an alanine at position 1060 (i.e., mutation S1060A), just 2 residues downstream of the M1058 that is changed in most FIPVs. All other FIPVs and all sequenced FECVs consistently had a serine at this position. The difference is brought about in all 5 cases by a T→G change at nucleotide 23537. Overall, we have detected characteristic differences with FECV for 113 (95.8%) of the 118 sequenced FIPVs. These differences were observed in both pathologic forms (i.e., wet and dry forms) of feline infectious peritonitis (Table 2).


Spike protein fusion peptide and feline coronavirus virulence.

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

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.
© Copyright Policy
Related In: Results  -  Collection

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

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.
Mentions: Assuming that the difference observed in 108 of the 118 sequenced FIPVs may be responsible for the virulent phenotype, the remaining 10 viruses should be expected to carry alternative differences. In search of those differences, we performed a phylogenetic analysis of the partial nucleotide sequences accumulated by the RT-nPCR procedure, but the results did not enable further differentiation (data not shown). When carrying out a phylogenetic analysis of the translated partial amino acid sequences, we observed a small but distinct second cluster B in addition to the major cluster A constituted by the FIPVs having leucine at position 1058 in their S protein (Figure 3). This smaller cluster, formed by 5 (4.2%) of the sequenced FIPVs, appeared to be characterized by the occurrence of an alanine at position 1060 (i.e., mutation S1060A), just 2 residues downstream of the M1058 that is changed in most FIPVs. All other FIPVs and all sequenced FECVs consistently had a serine at this position. The difference is brought about in all 5 cases by a T→G change at nucleotide 23537. Overall, we have detected characteristic differences with FECV for 113 (95.8%) of the 118 sequenced FIPVs. These differences were observed in both pathologic forms (i.e., wet and dry forms) of feline infectious peritonitis (Table 2).

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