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Updated: May 18, 2026

Co-immunoprecipitation of the Mouse Mx1 Protein with the Influenza A Virus Nucleoprotein
Published on: April 21, 2015
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.
Abstract:
Mx1 is a GTPase that is part of the antiviral response induced by type I and type III interferons in the infected host. It inhibits influenza virus infection by blocking viral transcription and replication, but the molecular mechanism is not known. Polymerase basic protein 2 (PB2) and nucleoprotein (NP) were suggested to be the possible target of Mx1, but a direct interaction between Mx1 and any of the viral proteins has not been reported. We investigated the interplay between Mx1, NP, and PB2 to identify the mechanism of Mx1's antiviral activity. We found that Mx1 inhibits the PB2-NP interaction, and the strength of this inhibition correlated with a decrease in viral polymerase activity. Inhibition of the PB2-NP interaction is an active process requiring enzymatically active Mx1. We also demonstrate that Mx1 interacts with the viral proteins NP and PB2, which indicates that Mx1 protein has a direct effect on the viral ribonucleoprotein complex. In a minireplicon system, avian-like NP from swine virus isolates was more sensitive to inhibition by murine Mx1 than NP from human influenza A virus isolates. Likewise, murine Mx1 displaced avian NP from the viral ribonucleoprotein complex more easily than human NP. The stronger resistance of the A/H1N1 pandemic 2009 virus against Mx1 also correlated with reduced inhibition of the PB2-NP interaction. Our findings support a model in which Mx1 interacts with the influenza ribonucleoprotein complex and interferes with its assembly by disturbing the PB2-NP interaction.
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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