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J Gen Virol. 2017 Jun;98(6):1174-1180. doi: 10.1099/jgv.0.000796. Epub 2017 Jun 14.

Mutations in the fusion protein heptad repeat domains of human metapneumovirus impact on the formation of syncytia.

Author information

1
1​Centre de Recherche en Infectiologie of the Centre Hospitalier Universitaire de Québec and Université Laval, Québec, Canada 2​Laboratoire de Virologie et Pathologie Humaine - VirPath Team, Centre International de Recherche en Infectiologie CIRI, Inserm U1111, CNRS UMR5308, ENS Lyon, Université Claude Bernard Lyon 1, Lyon, France.
2
1​Centre de Recherche en Infectiologie of the Centre Hospitalier Universitaire de Québec and Université Laval, Québec, Canada.
3
2​Laboratoire de Virologie et Pathologie Humaine - VirPath Team, Centre International de Recherche en Infectiologie CIRI, Inserm U1111, CNRS UMR5308, ENS Lyon, Université Claude Bernard Lyon 1, Lyon, France.
4
2​Laboratoire de Virologie et Pathologie Humaine - VirPath Team, Centre International de Recherche en Infectiologie CIRI, Inserm U1111, CNRS UMR5308, ENS Lyon, Université Claude Bernard Lyon 1, Lyon, France 3​Hospices Civils de Lyon, Centre National de Référence Virus Influenzae France Sud, Laboratoire de Virologie, Groupement Hospitalier Nord, F-69317, Lyon, France.
5
4​Institut de Biologie Intégrative et des Systèmes (IBIS), Université Laval, Pavillon Charles-Eugene-Marchand, Québec, Canada 5​Département de Biochimie, de Microbiologie et de Bio-informatique, PROTEO, Université Laval, Québec, Canada.

Abstract

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.

PMID:
28613142
DOI:
10.1099/jgv.0.000796
[Indexed for MEDLINE]

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