Influenza A Virus Nucleoprotein Activates the JNK Stress-Signaling Pathway for Viral Replication by Sequestering Host Filamin A Protein

摘要: Influenza A virus (IAV) poses a major threat to global public health and is known employ various strategies usurp the host machinery for survival. Due its fast-evolving nature, IAVs tend escape effect of available drugs vaccines thus, prompting development novel antiviral strategies. High-throughput mass spectrometric screen host-IAV interacting partners revealed Filamin (FLNA), an actin-binding protein involved in regulating multiple signaling pathways, as interaction partner IAV nucleoprotein (NP). In this study, we found that NP interrupts FLNA-TRAF2 by with FLNA resulting increased levels free, displaced TRAF2 molecules TRAF2-ASK1 mediated JNK pathway activation, critical maintaining efficient viral replication. addition, siRNA-mediated silencing was promote replication (87% increase) while FLNA-overexpression impaired (65% decrease). observed be crucial factor required attain mRNA attenuation post-IAV infection Our results reveal potential hitherto unknown cycle opening new possibilities FLNA-NP candidate anti-influenza drug target.