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Chemical-controlled activation of antiviral myxovirus resistance protein 1

(2017) JOURNAL OF BIOLOGICAL CHEMISTRY. 292(6). p.2226-2236
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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.
Keywords
INFLUENZA-A VIRUS, MX-PROTEINS, OLIGOMERIZATION, OVEREXPRESSION, REQUIREMENTS, SENSITIVITY, POLYMERASE, RAPAMYCIN, REVEALS, TARGET

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Chicago
Verhelst, Judith, Lien Van Hoecke, Jan Spitaels, Dorien De Vlieger, Annasaheb Kolpe, and Xavier Saelens. 2017. “Chemical-controlled Activation of Antiviral Myxovirus Resistance Protein 1.” Journal of Biological Chemistry 292 (6): 2226–2236.
APA
Verhelst, Judith, Van Hoecke, L., Spitaels, J., De Vlieger, D., Kolpe, A., & Saelens, X. (2017). Chemical-controlled activation of antiviral myxovirus resistance protein 1. JOURNAL OF BIOLOGICAL CHEMISTRY, 292(6), 2226–2236.
Vancouver
1.
Verhelst J, Van Hoecke L, Spitaels J, De Vlieger D, Kolpe A, Saelens X. Chemical-controlled activation of antiviral myxovirus resistance protein 1. JOURNAL OF BIOLOGICAL CHEMISTRY. 2017;292(6):2226–36.
MLA
Verhelst, Judith, Lien Van Hoecke, Jan Spitaels, et al. “Chemical-controlled Activation of Antiviral Myxovirus Resistance Protein 1.” JOURNAL OF BIOLOGICAL CHEMISTRY 292.6 (2017): 2226–2236. Print.
@article{8512265,
  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.},
  author       = {Verhelst, Judith and Van Hoecke, Lien and Spitaels, Jan and De Vlieger, Dorien and Kolpe, Annasaheb and Saelens, Xavier},
  issn         = {0021-9258},
  journal      = {JOURNAL OF BIOLOGICAL CHEMISTRY},
  keyword      = {INFLUENZA-A VIRUS,MX-PROTEINS,OLIGOMERIZATION,OVEREXPRESSION,REQUIREMENTS,SENSITIVITY,POLYMERASE,RAPAMYCIN,REVEALS,TARGET},
  language     = {eng},
  number       = {6},
  pages        = {2226--2236},
  title        = {Chemical-controlled activation of antiviral myxovirus resistance protein 1},
  url          = {http://dx.doi.org/10.1074/jbc.m116.748806},
  volume       = {292},
  year         = {2017},
}

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