The nucleoprotein of influenza A virus inhibits the innate immune response by inducing mitophagy

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Updated: Aug 15, 2025

Affinity Purification of Influenza Virus Ribonucleoprotein Complexes from the Chromatin of Infected Cells
11:20

Affinity Purification of Influenza Virus Ribonucleoprotein Complexes from the Chromatin of Infected Cells

Published on: June 3, 2012

13.2K

Bo Zhang1,2, Shuai Xu1, Minxuan Liu1,2

  • 1State Key Laboratory of Veterinary Etiological Biology, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, PR China.

Autophagy
|January 2, 2023
PubMed

Insights

Influenza virus nucleoprotein (NP) hijacks mitophagy to degrade MAVS, blocking antiviral defenses and promoting viral replication. A specific NP mutation (Y313F) impairs this process, reducing viral spread.

Area of Science:

  • Cell Biology
  • Virology
  • Immunology

Background:

  • Mitophagy, a selective form of autophagy, is crucial for mitochondrial quality control.
  • Viruses exploit cellular processes, including mitophagy, to evade host immunity and facilitate replication.

Purpose of the Study:

  • To investigate the role of H1N1 influenza virus nucleoprotein (NP) in regulating mitophagy.
  • To elucidate the mechanism by which NP manipulates mitophagy to promote viral replication and inhibit antiviral responses.

Main Methods:

  • Co-immunoprecipitation assays to identify protein interactions.
  • Western blotting and microscopy to assess mitophagy and protein degradation.
  • Viral replication assays in vitro and in vivo.
  • Site-directed mutagenesis to study the role of specific NP residues.

Main Results:

  • H1N1 virus NP was identified as a regulator of mitophagy.
  • NP induces mitophagy, leading to the degradation of mitochondrial antiviral signaling protein (MAVS).
  • This degradation blocks MAVS-mediated antiviral signaling, promoting influenza A virus (IAV) replication.
  • The interaction between NP and MAVS, mediated by cargo receptor TOLLIP, is essential for NP-induced mitophagy.
  • A key residue, Y313 in NP, is critical for MAVS-NP interaction and mitophagy induction.
  • Mutation of Y313 to Phenylalanine (NPY313F) significantly reduces virus-induced mitophagy and viral replication.

Conclusions:

  • Influenza virus NP utilizes mitophagy as a novel mechanism to suppress innate immunity.
  • NP-mediated degradation of MAVS through mitophagy is a key viral strategy to attenuate host antiviral defenses.
  • Targeting the NP-MAVS interaction or NP-mediated mitophagy could be a potential therapeutic strategy against influenza infections.
Keywords:
Influenza A virusMAVSTOLLIPmitophagynucleoprotein

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