title: Chemical-controlled Activation of Antiviral Myxovirus Resistance Protein 1.
abstract: The antiviral myxovirus resistance protein 1 (MX1) is an interferon-induced GTPase that plays an important role in the defense of mammalian cells against influenza A viruses. Mouse MX1 interacts with the influenza ribonucleoprotein complexes (vRNPs) and can prevent the interaction between polymerase basic 2 (PB2) and the nucleoprotein (NP) of influenza A viruses. However, it is unclear whether mouse MX1 disrupts the PB2-NP interaction in the context of pre-existing vRNPs or prevents the assembly of new vRNP components. Here, we describe a conditionally active mouse MX1 variant that only exerts antiviral activity in the presence of a small molecule drug. Once activated, this MX1 construct phenocopies the antiviral and NP binding activity of wild type MX1. The interaction between PB2 and NP is disrupted within minutes after the addition of the small molecule activator. These findings support a model in which mouse MX1 interacts with the incoming influenza A vRNPs and inhibits their activity by disrupting the PB2-NP interaction.
authors.affiliation: From the Medical Biotechnology Center, VIB, 9052 Ghent and.|the Department of Biomedical Molecular Biology, Ghent University, 9052 Ghent, Belgium.
authors.forename: Judith
authors.initials: J
authors.lastname: Verhelst
authors.affiliation: From the Medical Biotechnology Center, VIB, 9052 Ghent and.|the Department of Biomedical Molecular Biology, Ghent University, 9052 Ghent, Belgium.
authors.forename: Lien
authors.initials: L
authors.lastname: Van Hoecke
authors.affiliation: From the Medical Biotechnology Center, VIB, 9052 Ghent and.|the Department of Biomedical Molecular Biology, Ghent University, 9052 Ghent, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Spitaels
authors.affiliation: From the Medical Biotechnology Center, VIB, 9052 Ghent and.|the Department of Biomedical Molecular Biology, Ghent University, 9052 Ghent, Belgium.
authors.forename: Dorien
authors.initials: D
authors.lastname: De Vlieger
authors.affiliation: From the Medical Biotechnology Center, VIB, 9052 Ghent and.|the Department of Biomedical Molecular Biology, Ghent University, 9052 Ghent, Belgium.
authors.forename: Annasaheb
authors.initials: A
authors.lastname: Kolpe
authors.affiliation: From the Medical Biotechnology Center, VIB, 9052 Ghent and xavier.saelens@vib-ugent.be.|the Department of Biomedical Molecular Biology, Ghent University, 9052 Ghent, Belgium.
authors.forename: Xavier
authors.identifier: 0000-0002-3861-6965
authors.initials: X
authors.lastname: Saelens
mesh_terms: D000818:Animals; D019281:Dimerization; D004285:Dogs; D057809:HEK293 Cells; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000378:metabolism / Q000502:physiology; D061985:Madin Darby Canine Kidney Cells; D051379:Mice; D064547:Myxovirus Resistance Proteins / Q000378:metabolism*; D011485:Protein Binding; D012261:Ribonucleoproteins / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism; D014779:Virus Replication
chemical_list: D064547:Myxovirus Resistance Proteins; D012261:Ribonucleoproteins
keywords: GTPase; MX1; antiviral agent; influenza A; influenza virus; inhibition mechanism; interaction; molecular biology; negative-strand RNA virus; ribonucleoprotein; viral replication; virology