Mutations in the Fusion Protein Cleavage Site of Avian Paramyxovirus Serotype 4 Confer Increased Replication and Syncytium Formation In Vitro but Not Increased Replication and Pathogenicity in Chickens and Ducks

Autor: Shin-Hee Kim, Sa Xiao, Heather R. Shive, Peter L. Collins, Siba K. Samal
Rok vydání: 2013
Předmět:
viruses
Veterinary Microbiology
Mutant
lcsh:Medicine
Antibodies
Viral
Virus Replication
Giant Cells
Cytopathogenic Effect
Viral
Molecular Cell Biology
Avulavirus
lcsh:Science
Peptide sequence
Animal Management
Neurons
Syncytium
Multidisciplinary
biology
Brain
Immunohistochemistry
Ducks
Veterinary Diseases
Veterinary Pathology
Research Article
Veterinary Medicine
Histology
animal structures
Animal Types
Molecular Sequence Data
Cleavage (embryo)
Microbiology
Virus
Veterinary Epidemiology
Cell Line
Virology
Genetics
Animals
Humans
Amino Acid Sequence
Serotyping
Biology
Tropism
Evolutionary Biology
Base Sequence
Avulavirus Infections
lcsh:R
Virion
Veterinary Virology
biology.organism_classification
Reverse Genetics
Retraction
Kinetics
Viral replication
Mutation
Proteolysis
Veterinary Science
Mutant Proteins
lcsh:Q
Chickens
Viral Fusion Proteins
Zdroj: PLoS ONE, Vol 8, Iss 1, p e50598 (2013)
PLoS ONE
ISSN: 1932-6203
Popis: To evaluate the role of the F protein cleavage site in the replication and pathogenicity of avian paramyxoviruses (APMVs), we constructed a reverse genetics system for recovery of infectious recombinant APMV-4 from cloned cDNA. The recovered recombinant APMV-4 resembled the biological virus in growth characteristics in vitro and in pathogenicity in vivo. The F cleavage site sequence of APMV-4 (DIQPR↓F) contains a single basic amino acid, at the -1 position. Six mutant APMV-4 viruses were recovered in which the F protein cleavage site was mutated to contain increased numbers of basic amino acids or to mimic the naturally occurring cleavage sites of several paramyxoviruses, including neurovirulent and avirulent strains of NDV. The presence of a glutamine residue at the -3 position was found to be important for mutant virus recovery. In addition, cleavage sites containing the furin protease motif conferred increased replication and syncytium formation in vitro. However, analysis of viral pathogenicity in 9-day-old embryonated chicken eggs, 1-day-old and 2-week-old chickens, and 3-week-old ducks showed that none the F protein cleavage site mutations altered the replication, tropism, and pathogenicity of APMV-4, and no significant differences were observed among the parental and mutant APMV-4 viruses in vivo. Although parental and mutant viruses replicated somewhat better in ducks than in chickens, they all were highly restricted and avirulent in both species. These results suggested that the cleavage site sequence of the F protein is not a limiting determinant of APMV-4 pathogenicity in chickens and ducks.
Databáze: OpenAIRE
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