Integrin αvβ1 Modulation Affects Subtype B Avian Metapneumovirus Fusion Protein-mediated Cell-Cell Fusion and Virus Infection

Avian metapneumovirus (aMPV) fusion (F) protein mediates virus-cell membrane fusion to initiate viral infection, which requires F protein binding to its receptor(s) on the host cell surface. However, the receptor(s) for aMPV F protein is still not identified. All known subtype B aMPV (aMPV/B) F prot...

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Published in:The Journal of biological chemistry 2016-07, Vol.291 (28), p.14815-14825
Main Authors: Yun, Bing-Ling, Guan, Xiao-Lu, Liu, Yong-Zhen, Zhang, Yao, Wang, Yong-Qiang, Qi, Xiao-Le, Cui, Hong-Yu, Liu, Chang-Jun, Zhang, Yan-Ping, Gao, Hong-Lei, Gao, Li, Li, Kai, Gao, Yu-Long, Wang, Xiao-Mei
Format: Article
Language:English
Subjects:
aMPV/B, fusogenicity
Animals
Cell Fusion
Cell Line
fusion protein
infection
integrin
membrane fusion
Metapneumovirus - physiology
Microbiology
Paramyxoviridae Infections - physiopathology
Paramyxoviridae Infections - virology
Receptors, Vitronectin - physiology
Viral Fusion Proteins - physiology
viral replication
Virus Replication
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Summary:Avian metapneumovirus (aMPV) fusion (F) protein mediates virus-cell membrane fusion to initiate viral infection, which requires F protein binding to its receptor(s) on the host cell surface. However, the receptor(s) for aMPV F protein is still not identified. All known subtype B aMPV (aMPV/B) F proteins contain a conserved Arg-Asp-Asp (RDD) motif, suggesting that the aMPV/B F protein may mediate membrane fusion via the binding of RDD to integrin. When blocked with integrin-specific peptides, aMPV/B F protein fusogenicity and viral replication were significantly reduced. Specifically we identified integrin αv and/or β1-mediated F protein fusogenicity and viral replication using antibody blocking, small interfering RNAs (siRNAs) knockdown, and overexpression. Additionally, overexpression of integrin αv and β1 in aMPV/B non-permissive cells conferred aMPV/B F protein binding and aMPV/B infection. When RDD was altered to RAE (Arg-Ala-Glu), aMPV/B F protein binding and fusogenic activity were profoundly impaired. These results suggest that integrin αvβ1 is a functional receptor for aMPV/B F protein-mediated membrane fusion and virus infection, which will provide new insights on the fusogenic mechanism and pathogenesis of aMPV.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M115.711382