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https://doi.org/10.3389/fmicb.2020.581867
Title: | Influenza A Virus Nucleoprotein Activates the JNK Stress-Signaling Pathway for Viral Replication by Sequestering Host Filamin A Protein | Authors: | Sharma, A. Batra, J. Stuchlik, O. Reed, M.S. Pohl, J. Chow, V.T.K. Sambhara, S. Lal, S.K. |
Keywords: | actin-binding proteins host-virus interaction IAV replication next generation anti-influenza target protein-protein interaction |
Issue Date: | 2020 | Publisher: | Frontiers Media S.A. | Citation: | Sharma, A., Batra, J., Stuchlik, O., Reed, M.S., Pohl, J., Chow, V.T.K., Sambhara, S., Lal, S.K. (2020). Influenza A Virus Nucleoprotein Activates the JNK Stress-Signaling Pathway for Viral Replication by Sequestering Host Filamin A Protein. Frontiers in Microbiology 11 : 581867. ScholarBank@NUS Repository. https://doi.org/10.3389/fmicb.2020.581867 | Rights: | Attribution 4.0 International | Abstract: | Influenza A virus (IAV) poses a major threat to global public health and is known to employ various strategies to usurp the host machinery for survival. Due to its fast-evolving nature, IAVs tend to escape the effect of available drugs and vaccines thus, prompting the development of novel antiviral strategies. High-throughput mass spectrometric screen of host-IAV interacting partners revealed host Filamin A (FLNA), an actin-binding protein involved in regulating multiple signaling pathways, as an interaction partner of IAV nucleoprotein (NP). In this study, we found that the IAV NP interrupts host FLNA-TRAF2 interaction by interacting with FLNA thus, resulting in increased levels of free, displaced TRAF2 molecules available for TRAF2-ASK1 mediated JNK pathway activation, a pathway critical to maintaining efficient viral replication. In addition, siRNA-mediated FLNA silencing was found to promote IAV replication (87% increase) while FLNA-overexpression impaired IAV replication (65% decrease). IAV NP was observed to be a crucial viral factor required to attain FLNA mRNA and protein attenuation post-IAV infection for efficient viral replication. Our results reveal FLNA to be a host factor with antiviral potential hitherto unknown to be involved in the IAV replication cycle thus, opening new possibilities of FLNA-NP interaction as a candidate anti-influenza drug development target. © Copyright © 2020 Sharma, Batra, Stuchlik, Reed, Pohl, Chow, Sambhara and Lal. | Source Title: | Frontiers in Microbiology | URI: | https://scholarbank.nus.edu.sg/handle/10635/197468 | ISSN: | 1664302X | DOI: | 10.3389/fmicb.2020.581867 | Rights: | Attribution 4.0 International |
Appears in Collections: | Staff Publications Elements |
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