Influenza A virus nucleoprotein activates the JNK stress-signaling pathway for viral replication by sequestering host filamin A protein

Anshika Sharma, Jyoti Batra, Olga Stuchlik, Matthew S. Reed, Jan Pohl, Vincent T.K. Chow, Suryaprakash Sambhara, Sunil K. Lal

    Research output: Contribution to journalArticleResearchpeer-review

    2 Citations (Scopus)

    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.

    Original languageEnglish
    Article number581867
    Number of pages17
    JournalFrontiers in Microbiology
    Volume11
    DOIs
    Publication statusPublished - 25 Sep 2020

    Keywords

    • actin-binding proteins
    • host-virus interaction
    • IAV replication
    • next generation anti-influenza target
    • protein-protein interaction

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