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

作者：Dubois Julia; Cavanagh Marie Helene; Terrier Olivier; Hamelin Marie Eve; Lina Bruno; Shi Rong; Rosa Calatrava Manuel; Boivin Guy^*

来源：Journal of General Virology, 2017, 98(6): 1174-1180.

DOI：10.1099/jgv.0.000796

• human metapneumovirus
• fusion protein
• heptad repeat
• cell fusion

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 Al/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-6139N T143K-K166E-E167D in HRA and/or K479R-N4825 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.

• 出版日期2017-6