tetano
Editor, Senior Moderator
Virology. 2017 Dec 14;514:230-239. doi: 10.1016/j.virol.2017.11.004. [Epub ahead of print]
[h=1]Inhibition of neddylation pathway represses influenza virus replication and pro-inflammatory responses.[/h] Sun H[SUP]1[/SUP], Yao W[SUP]2[/SUP], Wang K[SUP]2[/SUP], Qian Y[SUP]3[/SUP], Chen H[SUP]4[/SUP], Jung YS[SUP]5[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] The neddylation pathway belongs post-translational modifications and plays important roles in regulating viral infection and replication. To address the relationship of influenza A virus with the neddylation modification pathway, we demonstrate that IAV infection in A549 cells can activate the neddylation modification pathway to increase virus growth and enhance the expression of pro-inflammatory cytokines to increase pathogenicity. The pre-treatment of Nedd8-activating enzyme subunit 1 (NAE1)-specific inhibitor, MLN4924, interferes with Nedd8 conjugation and NF-κB activity. MLN4924 exhibited pronounced antiviral activity against different subtypes of influenza A virus, including classical H1N1 (PR8), H9N2 subtype, and pandemic H1N1 2009 (pdmH1N1) viruses. Through the inhibition of the CRL/NF-κB pathway, MLN4924 could significantly suppress the expression levels of pro-inflammatory cytokines induced by IAVs. These findings suggest that MLN4924 can be developed as a novel antiviral therapy for influenza infection for anti-viral efficacy and anti-inflammation activity.
[h=4]KEYWORDS:[/h] Influenza A virus; MLN4924; Neddylation; Pro-inflammatory cytokine
PMID: 29248752 DOI: 10.1016/j.virol.2017.11.004
[h=1]Inhibition of neddylation pathway represses influenza virus replication and pro-inflammatory responses.[/h] Sun H[SUP]1[/SUP], Yao W[SUP]2[/SUP], Wang K[SUP]2[/SUP], Qian Y[SUP]3[/SUP], Chen H[SUP]4[/SUP], Jung YS[SUP]5[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] The neddylation pathway belongs post-translational modifications and plays important roles in regulating viral infection and replication. To address the relationship of influenza A virus with the neddylation modification pathway, we demonstrate that IAV infection in A549 cells can activate the neddylation modification pathway to increase virus growth and enhance the expression of pro-inflammatory cytokines to increase pathogenicity. The pre-treatment of Nedd8-activating enzyme subunit 1 (NAE1)-specific inhibitor, MLN4924, interferes with Nedd8 conjugation and NF-κB activity. MLN4924 exhibited pronounced antiviral activity against different subtypes of influenza A virus, including classical H1N1 (PR8), H9N2 subtype, and pandemic H1N1 2009 (pdmH1N1) viruses. Through the inhibition of the CRL/NF-κB pathway, MLN4924 could significantly suppress the expression levels of pro-inflammatory cytokines induced by IAVs. These findings suggest that MLN4924 can be developed as a novel antiviral therapy for influenza infection for anti-viral efficacy and anti-inflammation activity.
[h=4]KEYWORDS:[/h] Influenza A virus; MLN4924; Neddylation; Pro-inflammatory cytokine
PMID: 29248752 DOI: 10.1016/j.virol.2017.11.004