Interferon-inducible protein Mx1 inhibits influenza virus by interfering with functional viral ribonucleoprotein

Judith Verhelst1, Eef Parthoens, Bert Schepens

  • 1Department for Molecular Biomedical Research, VIB, Ghent, Belgium.

Journal of Virology
|September 28, 2012
PubMed

Insights

Mx1 protein inhibits influenza virus by blocking viral transcription and replication. It directly interacts with viral proteins, disrupting the PB2-NP interaction essential for viral polymerase activity.

Area of Science:

  • Virology
  • Immunology
  • Molecular Biology

Background:

  • Mx1 is a GTPase involved in the host's antiviral response to interferons.
  • Mx1 inhibits influenza virus but its molecular mechanism remains unclear.
  • Previous studies suggested PB2 and NP as potential targets, but direct interaction was not confirmed.

Purpose of the Study:

  • To investigate the interaction between Mx1, PB2, and NP to elucidate Mx1's antiviral mechanism.
  • To determine if Mx1 directly interacts with viral proteins.
  • To understand how Mx1 affects viral polymerase activity.

Main Methods:

  • Investigated the interplay between Mx1, NP, and PB2.
  • Assessed viral polymerase activity.
  • Utilized a minireplicon system to compare inhibition sensitivity.
  • Analyzed Mx1's interaction with the viral ribonucleoprotein complex.

Main Results:

  • Mx1 inhibits the interaction between PB2 and NP, correlating with reduced viral polymerase activity.
  • Mx1 directly interacts with NP and PB2, affecting the viral ribonucleoprotein complex.
  • Avian-like NP is more sensitive to murine Mx1 inhibition than human NP.
  • A/H1N1 pandemic virus showed resistance to Mx1 due to reduced PB2-NP interaction inhibition.

Conclusions:

  • Mx1 interferes with influenza virus assembly by disrupting the PB2-NP interaction.
  • Mx1 directly targets the viral ribonucleoprotein complex.
  • Understanding Mx1-viral protein interactions can inform antiviral strategies.

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