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 |
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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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