Limits...
Genetics and pathogenesis of feline infectious peritonitis virus.

Brown MA, Troyer JL, Pecon-Slattery J, Roelke ME, O'Brien SJ - Emerging Infect. Dis. (2009)

Bottom Line: Uncertainty remains regarding whether genetically distinctive avirulent and virulent forms coexist or whether an avirulent form mutates in vivo, causing FIP.These data demonstrate distinctive circulating virulent and avirulent strains in natural populations.These findings may have potential as diagnostic markers for virulent FIP-associated FCoV.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Genomic Diversity, National Cancer Institute, Frederick, Maryland 21702, USA. brownmer@gmail.com

ABSTRACT
Feline coronavirus (FCoV) is endemic in feral cat populations and cat colonies, frequently preceding outbreaks of fatal feline infectious peritonitis (FIP). FCoV exhibits 2 biotypes: the pathogenic disease and a benign infection with feline enteric coronavirus (FECV). Uncertainty remains regarding whether genetically distinctive avirulent and virulent forms coexist or whether an avirulent form mutates in vivo, causing FIP. To resolve these alternative hypotheses, we isolated viral sequences from FCoV-infected clinically healthy and sick cats (8 FIP cases and 48 FECV-asymptomatic animals); 735 sequences from 4 gene segments were generated and subjected to phylogenetic analyses. Viral sequences from healthy cats were distinct from sick cats on the basis of genetic distances observed in the membrane and nonstructural protein 7b genes. These data demonstrate distinctive circulating virulent and avirulent strains in natural populations. In addition, 5 membrane protein amino acid residues with functional potential differentiated healthy cats from cats with FIP. These findings may have potential as diagnostic markers for virulent FIP-associated FCoV.

Show MeSH

Related in: MedlinePlus

Diagram of membrane protein containing 3 transmembrane helices, an external N terminus and an internal carboxy terminus. Approximate position of 5 variable diagnostic amino acid sites (see Table 2) as determined by sequence comparison to severe acute respiratory syndrome coronavirus (32). Amino acid residue, polarity, and hydrophobicity or hydropholicity is stated.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2819880&req=5

Figure 5: Diagram of membrane protein containing 3 transmembrane helices, an external N terminus and an internal carboxy terminus. Approximate position of 5 variable diagnostic amino acid sites (see Table 2) as determined by sequence comparison to severe acute respiratory syndrome coronavirus (32). Amino acid residue, polarity, and hydrophobicity or hydropholicity is stated.

Mentions: A role of the membrane protein in FIP pathogenesis seems likely, given its known functions in other coronaviruses. The membrane protein is the most abundant structural protein with important functions in virus budding and with cell-mediated host immunity (31). The specific functions of the membrane protein amino acid sequences have been determined in severe acute respiratory syndrome (SARS)–CoV (32). Aligning the sequences from this study with SARS-CoV, the first diagnostic amino acid site 108 aligns to a site just upstream from the second transmembrane helix (Appendix Figure 1). A tyrosine at position 108, which is found in all FIPV biotypes and shared among SARS-CoV, has a neutral polarity (in contrast to a histidine there, found in most FECV biotypes, which have a positive polarity) and may play a role in the stability of the virus within the membrane. Site 120 aligns within the third transmembrane helix, site 138 aligns just downstream to the transmembrane helice, site 163 aligns within the C-terminus, which projects inside the virus particle, and site 199, also within the C-terminus domain, aligns within a defined SARS-immunodominant epitope (32) (Figure 5).


Genetics and pathogenesis of feline infectious peritonitis virus.

Brown MA, Troyer JL, Pecon-Slattery J, Roelke ME, O'Brien SJ - Emerging Infect. Dis. (2009)

Diagram of membrane protein containing 3 transmembrane helices, an external N terminus and an internal carboxy terminus. Approximate position of 5 variable diagnostic amino acid sites (see Table 2) as determined by sequence comparison to severe acute respiratory syndrome coronavirus (32). Amino acid residue, polarity, and hydrophobicity or hydropholicity is stated.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2819880&req=5

Figure 5: Diagram of membrane protein containing 3 transmembrane helices, an external N terminus and an internal carboxy terminus. Approximate position of 5 variable diagnostic amino acid sites (see Table 2) as determined by sequence comparison to severe acute respiratory syndrome coronavirus (32). Amino acid residue, polarity, and hydrophobicity or hydropholicity is stated.
Mentions: A role of the membrane protein in FIP pathogenesis seems likely, given its known functions in other coronaviruses. The membrane protein is the most abundant structural protein with important functions in virus budding and with cell-mediated host immunity (31). The specific functions of the membrane protein amino acid sequences have been determined in severe acute respiratory syndrome (SARS)–CoV (32). Aligning the sequences from this study with SARS-CoV, the first diagnostic amino acid site 108 aligns to a site just upstream from the second transmembrane helix (Appendix Figure 1). A tyrosine at position 108, which is found in all FIPV biotypes and shared among SARS-CoV, has a neutral polarity (in contrast to a histidine there, found in most FECV biotypes, which have a positive polarity) and may play a role in the stability of the virus within the membrane. Site 120 aligns within the third transmembrane helix, site 138 aligns just downstream to the transmembrane helice, site 163 aligns within the C-terminus, which projects inside the virus particle, and site 199, also within the C-terminus domain, aligns within a defined SARS-immunodominant epitope (32) (Figure 5).

Bottom Line: Uncertainty remains regarding whether genetically distinctive avirulent and virulent forms coexist or whether an avirulent form mutates in vivo, causing FIP.These data demonstrate distinctive circulating virulent and avirulent strains in natural populations.These findings may have potential as diagnostic markers for virulent FIP-associated FCoV.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Genomic Diversity, National Cancer Institute, Frederick, Maryland 21702, USA. brownmer@gmail.com

ABSTRACT
Feline coronavirus (FCoV) is endemic in feral cat populations and cat colonies, frequently preceding outbreaks of fatal feline infectious peritonitis (FIP). FCoV exhibits 2 biotypes: the pathogenic disease and a benign infection with feline enteric coronavirus (FECV). Uncertainty remains regarding whether genetically distinctive avirulent and virulent forms coexist or whether an avirulent form mutates in vivo, causing FIP. To resolve these alternative hypotheses, we isolated viral sequences from FCoV-infected clinically healthy and sick cats (8 FIP cases and 48 FECV-asymptomatic animals); 735 sequences from 4 gene segments were generated and subjected to phylogenetic analyses. Viral sequences from healthy cats were distinct from sick cats on the basis of genetic distances observed in the membrane and nonstructural protein 7b genes. These data demonstrate distinctive circulating virulent and avirulent strains in natural populations. In addition, 5 membrane protein amino acid residues with functional potential differentiated healthy cats from cats with FIP. These findings may have potential as diagnostic markers for virulent FIP-associated FCoV.

Show MeSH
Related in: MedlinePlus