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Updated: Sep 3, 2025
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Co-immunoprecipitation of the Mouse Mx1 Protein with the Influenza A Virus Nucleoprotein
Published on: April 21, 2015
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MX2 Viral Substrate Breadth and Inhibitory Activity Are Regulated by Protein Phosphorylation
Gilberto Betancor1, Madeleine Bangham1, Jun Ki Jeon1
1Department of Infectious Diseases, School of Immunology and Microbial Sciences, King's College London, London, England.
Mbio
|July 26, 2022
Summary
Human myxovirus resistance 2 (MX2) phosphorylation regulates its antiviral activity against HIV-1. Specific mutations enhance MX2 function, enabling inhibition of resistant HIV-1 strains and other retroviruses.
Area of Science:
- Virology
- Molecular Biology
- Immunology
Background:
- Human immunodeficiency virus type-1 (HIV-1) infection relies on nuclear import of viral DNA.
- Human myxovirus resistance 2 (MX2/MxB) protein inhibits HIV-1 by blocking viral DNA nuclear import.
- Previous studies identified inhibitory phosphorylation sites (Ser14, 17, 18) on MX2.
Purpose of the Study:
- To investigate the role of MX2 posttranslational modifications, specifically phosphorylation, in regulating antiviral activity.
- To identify key phosphorylation sites that enhance or reduce MX2's ability to inhibit HIV-1.
- To explore the potential of modified MX2 proteins against drug-resistant viral strains.
Main Methods:
- Systematic substitution of serine and threonine residues in MX2 with aspartic acid (mimicking phosphorylation) or alanine (mimicking unphosphorylation).
- Assay of antiviral activity of generated MX2 mutants against wild-type and mutant HIV-1.
- Testing of hypermorphic MX2 mutants against MX2-resistant retroviruses like EIAV and MLV.
Main Results:
- Mutations at Ser306, Thr334 (aspartic acid substitutions), and Thr343 (alanine substitution) reduced MX2 antiviral activity (hypomorphic).
- Mutations at Ser28, Thr151, and Thr343 (aspartic acid substitutions) enhanced MX2 activity (hypermorphic).
- Hypermorphic mutants inhibited wild-type HIV-1, HIV-1 capsid mutants (P90A, T210K), and MX2-resistant retroviruses (EIAV, MLV).
Conclusions:
- Phosphorylation status of MX2 is a critical regulator of its antiviral function and substrate specificity.
- Hypermorphic MX2 variants demonstrate broad-spectrum antiviral potential, including against resistant viral strains.
- MX2 phosphorylation dynamics offer a potential target for developing novel antiviral strategies.
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