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Chemical-controlled activation of antiviral Myxovirus Resistance 1.

Chemical-controlled activation of antiviral Myxovirus Resistance 1.
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Verhelst J, Van Hoecke L, Spitaels J, De Vlieger D, Kolpe A, Saelens X,


Verhelst J, Van Hoecke L, Spitaels J, De Vlieger D, Kolpe A, Saelens X, (click to view)

Verhelst J, Van Hoecke L, Spitaels J, De Vlieger D, Kolpe A, Saelens X,

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The Journal of biological chemistry 2016 12 23() pii jbc.M116.748806
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 if 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.

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