tetano
Editor, Senior Moderator
J Gen Virol. 2017 Jun 14. doi: 10.1099/jgv.0.000782. [Epub ahead of print]
[h=1]Influenza virus protein PB1-F2 interacts with CALCOCO2 (NDP52) to modulate innate immune response.[/h] Leymarie O[SUP]1[/SUP], Meyer L[SUP]1[/SUP], Tafforeau L[SUP]2[/SUP], Lotteau V[SUP]3[/SUP], Costa BD[SUP]1[/SUP], Delmas B[SUP]1[/SUP], Chevalier C[SUP]1[/SUP], Le Goffic R[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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 (Kd) 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-κB kinase/NF-κB signalling pathway. NF-κB 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-κB 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.
PMID: 28613140 DOI: 10.1099/jgv.0.000782
[h=1]Influenza virus protein PB1-F2 interacts with CALCOCO2 (NDP52) to modulate innate immune response.[/h] Leymarie O[SUP]1[/SUP], Meyer L[SUP]1[/SUP], Tafforeau L[SUP]2[/SUP], Lotteau V[SUP]3[/SUP], Costa BD[SUP]1[/SUP], Delmas B[SUP]1[/SUP], Chevalier C[SUP]1[/SUP], Le Goffic R[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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 (Kd) 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-κB kinase/NF-κB signalling pathway. NF-κB 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-κB 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.
PMID: 28613140 DOI: 10.1099/jgv.0.000782