Announcement

Collapse
No announcement yet.

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

Collapse
X
 
  • Filter
  • Time
  • Show
Clear All
new posts

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


    Front Microbiol


    . 2020 Sep 25;11:581867.
    doi: 10.3389/fmicb.2020.581867. eCollection 2020.
    Influenza A Virus Nucleoprotein Activates the JNK Stress-Signaling Pathway for Viral Replication by Sequestering Host Filamin A Protein


    Anshika Sharma 1 , Jyoti Batra 1 , Olga Stuchlik 2 , Matthew S Reed 2 , Jan Pohl 2 , Vincent T K Chow 3 , Suryaprakash Sambhara 4 , Sunil K Lal 1 5



    AffiliationsFree PMC article

    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.

    Keywords: IAV replication; actin-binding proteins; host-virus interaction; next generation anti-influenza target; protein-protein interaction.

Working...
X