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Mutations in the fusion protein heptad repeat domains of human metapneumovirus impact on the formation of syncytia
- Source :
- Journal of General Virology, Journal of General Virology, Microbiology Society, 2017, 98 (6), pp.1174-1180. ⟨10.1099/jgv.0.000796⟩, Journal of General Virology, 2017, 98 (6), pp.1174-1180. ⟨10.1099/jgv.0.000796⟩
- Publication Year :
- 2017
- Publisher :
- HAL CCSD, 2017.
-
Abstract
- International audience; Human metapneumovirus (HMPV) is an important cause of respiratory tract infections. The mechanism by which its fusion (F) protein is responsible for variable cytopathic effects in vitro remains unknown. We aligned the F sequences of the poorly fusogenic B2/CAN98-75 strain and the hyperfusogenic A1/C-85473 strain and identified divergent residues located in the two functional heptad repeats domains (HRA and HRB). We generated recombinant viruses by inserting the mutations N135T-G139N-T143K-K166E-E167D in HRA and/or K479R-N482S in HRB, corresponding to swapped sequences from C-85473, into CAN98-75 background and investigated their impact on in vitro phenotype and fusogenicity. We demonstrated that the five HRA mutations enhanced the fusogenicity of the recombinant rCAN98-75 virus, almost restoring the phenotype of the wild-type rC-85473 strain, whereas HRB substitutions alone had no significant effect on cell-cell fusion. Altogether, our results support the importance of the HRA domain for an HMPV-triggered fusion mechanism and identify key residues that modulate syncytium formation.
- Subjects :
- Models, Molecular
0301 basic medicine
Protein Conformation
viruses
Protein domain
DNA Mutational Analysis
Biology
medicine.disease_cause
Giant Cells
Cell Line
Cell Fusion
03 medical and health sciences
Human metapneumovirus
Protein Domains
Genetic
Models
Virology
medicine
Animals
Recombination, Genetic
Genetics
Mutation
Cell fusion
Molecular
Epithelial Cells
biology.organism_classification
Fusion protein
Phenotype
Macaca mulatta
[SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
Reverse genetics
Reverse Genetics
Recombination
3. Good health
Heptad repeat
030104 developmental biology
[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology
[SDV.IMM]Life Sciences [q-bio]/Immunology
Mutant Proteins
Metapneumovirus
Viral Fusion Proteins
Subjects
Details
- Language :
- English
- ISSN :
- 00221317 and 14652099
- Database :
- OpenAIRE
- Journal :
- Journal of General Virology, Journal of General Virology, Microbiology Society, 2017, 98 (6), pp.1174-1180. ⟨10.1099/jgv.0.000796⟩, Journal of General Virology, 2017, 98 (6), pp.1174-1180. ⟨10.1099/jgv.0.000796⟩
- Accession number :
- edsair.doi.dedup.....e5bd11b5504bbf39f5a889d6632c2936