1887

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Volume 98, Issue 6

Influenza virus protein PB1-F2 interacts with CALCOCO2 (NDP52) to modulate innate immune response Free

Abstract

PB1-F2 is a viral protein encoded by influenza A viruses (IAVs). PB1-F2 is implicated in virulence by triggering immune cell apoptosis and enhancing inflammation. To obtain an insight into the molecular mechanisms of PB1-F2-mediated virulence, we used the yeast two-hybrid approach to find new PB1-F2 cellular interactors. This allowed us to identify calcium-binding and coiled-coil domain 2 (CALCOCO2, also known as NDP52) as a binding partner of PB1-F2. Binding of PB1-F2 to CALCOCO2 was confirmed by pull-down. Surface plasmon resonance binding experiments enabled us to estimate the dissociation constant ( ) of the two partners to be around 20 nM. Using bioinformatics tools, we designed a CALCOCO2 interaction map based on previous knowledge and showed a strong connection between this protein and the type I interferon production pathways and the I-B kinase/NF-B signalling pathway. NF-B reporter assays in which CALCOCO2, MAVS and PB1-F2 were co-expressed showed a cooperation of these three proteins to increase the inflammatory response. By contrast, PB1-F2 inhibits the TBK1-dependent activation of an ISRE reporter plasmid. We also demonstrated that the signal transducer TRAF6 is implicated in the enhancement of NF-B activity mediated by PB1-F2/CALCOCO2 binding. Altogether, this report provides evidence of an interaction link between PB1-F2 and human proteins, and allows a better understanding of the involvement of PB1-F2 in the pathologic process mediated by IAV.

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Keyword(s): CALCOCO2 , influenza virus , innate immune response and PB1-F2
© 2017 The Authors
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2017-06-01
2024-04-19
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Influenza virus protein PB1-F2 interacts with CALCOCO2 (NDP52) to modulate innate immune response
J. Gen. Virol. 98, 1196 (2017); https://doi.org/10.1099/jgv.0.000782
/content/journal/jgv/10.1099/jgv.0.000782
/content/journal/jgv/10.1099/jgv.0.000782
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