Journal
VIROLOGY
Volume 514, Issue -, Pages 230-239Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2017.11.004
Keywords
Influenza A virus; Neddylation; MLN4924; Pro-inflammatory cytokine
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Funding
- National Natural Science Foundation of China [31572502]
- Fundamental Research Funds for the Central Universities [KYHW201702]
- Agricultural Science and Technology Innovation Program (ASTIP)
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
- National Key Research and Development Program of China [2017YFD0500702, 2017YFD0502302]
- Key project for Agriculture from Shanghai Agriculture Commission [201702080008F 00068]
- Priority Academic Program Development of Jiangsu Higher Education Institutions [PAPD-1]
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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-kappa B. 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-kappa B 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.
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