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Co-immunoprecipitation of the Mouse Mx1 Protein with the Influenza A Virus Nucleoprotein
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Mechanism of human MxA protein action: variants with changed antiviral properties

T Zürcher1, J Pavlovic, P Staeheli

  • 1Institute for Immunology and Virology, University of Zürich, Switzerland.

The EMBO Journal
|April 1, 1992
PubMed

Insights

A mutant human MxA protein (MxA(R645)) specifically inhibits influenza virus replication. Its antiviral activity and mechanism depend on cellular location, with nuclear MxA mimicking mouse Mx1 action.

Area of Science:

  • Virology
  • Cell Biology
  • Immunology

Background:

  • Interferon treatment induces Mx proteins that inhibit viral replication.
  • Human MxA is a cytoplasmic protein inhibiting influenza and vesicular stomatitis viruses.
  • Mx proteins can exist in nuclear or cytoplasmic forms with distinct functions.

Purpose of the Study:

  • To characterize a mutant human MxA protein (MxA(R645)) with altered antiviral specificity.
  • To investigate the effect of cellular localization (cytoplasmic vs. nuclear) on MxA's antiviral mechanism.
  • To identify regions of MxA responsible for determining antiviral specificity.

Main Methods:

  • Site-directed mutagenesis to create MxA(R645) mutant.
  • Transfection of cells with wild-type and mutant MxA constructs.
  • Assays to measure inhibition of influenza virus and vesicular stomatitis virus replication.
  • Localization studies using nuclear transport signals.

Main Results:

  • MxA(R645) inhibited influenza virus but not vesicular stomatitis virus, unlike wild-type MxA.
  • In the cytoplasm, MxA(R645) blocked influenza virus post-transcriptionally.
  • When localized to the nucleus, MxA(R645) inhibited influenza virus primary transcription, similar to mouse Mx1.

Conclusions:

  • A specific region near the MxA carboxy terminus dictates its antiviral specificity.
  • Nuclear localization alters MxA's antiviral mechanism, enabling it to inhibit viral transcription.
  • Nuclear MxA can functionally mimic nuclear Mx proteins like mouse Mx1.

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