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Updated: May 24, 2025

Identifying Caspases and their Motifs that Cleave Proteins During Influenza A Virus Infection
08:16

Identifying Caspases and their Motifs that Cleave Proteins During Influenza A Virus Infection

Published on: July 21, 2022

1.4K

Caspase cleavage of influenza A virus M2 disrupts M2-LC3 interaction and regulates virion production

Carmen Figueras-Novoa1,2, Masato Akutsu3,4, Daichi Murata3,5,6

  • 1Cell Biology of Infection Laboratory, The Francis Crick Institute, London, UK.

EMBO Reports
|March 3, 2025
PubMed

Insights

Influenza A virus M2 protein cleavage by caspases disrupts its interaction with LC3. This caspase-mediated regulation impacts viral egress and virion production, linking virus exit to host cell status.

Area of Science:

  • Virology
  • Molecular Biology
  • Structural Biology

Background:

  • Influenza A virus (IAV) Matrix 2 (M2) protein functions as an ion channel essential for viral entry and egress.
  • M2 interacts with the LC3 protein via its C-terminal LC3-interacting region (LIR).

Purpose of the Study:

  • To investigate the regulation of the M2-LC3 interaction by host proteases.
  • To elucidate the structural basis of M2-LC3 interaction and its modulation by cleavage.

Main Methods:

  • Caspase cleavage assays.
  • Crystal structure determination of M2 LIR in complex with LC3.
  • Analysis of IAV mutants expressing truncated M2 protein.

Main Results:

  • Caspase cleavage of M2 protein abolishes the M2-LC3 interaction.
  • The caspase cleavage motif (SAVD) is unstructured and distinct from the LIR.
  • IAV mutants with truncated M2 show defects in plasma membrane transport, viral filament formation, and virion production.

Conclusions:

  • Host caspases dynamically regulate the M2-LC3 interaction.
  • Cleavage of M2 by caspases is a critical mechanism influencing IAV exit and virion production.
  • This regulation connects viral particle release with the host cell's physiological state.
Keywords:
AutophagyCaspaseInfluenzaLC3M2

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