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Updated: Jun 12, 2025

Co-immunoprecipitation of the Mouse Mx1 Protein with the Influenza A Virus Nucleoprotein
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Co-immunoprecipitation of the Mouse Mx1 Protein with the Influenza A Virus Nucleoprotein

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Cellular NS1-BP protein interacts with the mRNA export receptor NXF1 to mediate nuclear export of influenza virus M

Ke Zhang1, Tolga Cagatay2, Dongqi Xie2

  • 1Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas, USA; Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences, Shanghai, China.

The Journal of Biological Chemistry
|October 9, 2024
PubMed

Insights

Influenza virus NS1 protein normally blocks mRNA export. However, NS1-binding protein (NS1-BP) facilitates M1 and M2 mRNA export by competing for export factors, enabling viral replication.

Area of Science:

  • Virology
  • Molecular Biology
  • Cell Biology

Background:

  • Influenza A viruses utilize host cell machinery for replication, including nuclear transcription and mRNA processing.
  • Viral non-structural protein 1 (NS1) interferes with host mRNA export, while NS1-binding protein (NS1-BP) promotes M1 to M2 splicing.
  • NS1 binds mRNA export receptor nuclear RNA export factor-1 (NXF1), inhibiting cellular mRNA export.

Purpose of the Study:

  • To elucidate the mechanism by which M1 and M2 mRNAs are exported from the nucleus despite NS1-mediated inhibition.
  • To investigate the role of NS1-BP in the nuclear export of viral M1 and M2 mRNAs.

Main Methods:

  • Biochemical assays to study protein-protein and protein-RNA interactions.
  • Cell biological techniques to visualize and track mRNA and protein localization within infected cells.
  • Analysis of viral replication in the presence and absence of key interacting proteins.

Main Results:

  • NS1-BP competes with NS1 for binding to NXF1, enabling NXF1 recruitment to M mRNAs.
  • The complex of NS1-BP, NS1, NXF1, and germinal center-associated nuclear protein facilitates M mRNA export.
  • Dissociation of viral proteins occurs at the nuclear pore complex, allowing M mRNA translocation to the cytoplasm.

Conclusions:

  • A novel pathway for viral mRNA nuclear export is described, overcoming NS1-mediated inhibition.
  • NS1-BP acts as a crucial viral host factor, mediating M mRNA export for viral replication.
  • Understanding these viral-host interactions is critical for developing antiviral strategies against influenza.
Keywords:
GANP (germinal center–associated nuclear protein)M1 (matrix protein 1 of influenza virus)NS1 (Non-Structural protein 1 of influenza A virus)NS1-BP (cellular NS1-binding protein)NXF1 (nuclear RNA export factor-1)NXT1 (nuclear transport factor 2–like export factor 1)TREX-2 (transcription and export complex-2)influenza virusmRNA export

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