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Chemical-controlled activation of antiviral myxovirus resistance protein 1

Judith Verhelst, Lien Van Hoecke UGent, Jan Spitaels UGent, Dorien De Vlieger UGent, Annasaheb Kolpe UGent and Xavier Saelens UGent (2017) JOURNAL OF BIOLOGICAL CHEMISTRY. 292(6). p.2226-2236
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.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
INFLUENZA-A VIRUS, MX-PROTEINS, OLIGOMERIZATION, OVEREXPRESSION, REQUIREMENTS, SENSITIVITY, POLYMERASE, RAPAMYCIN, REVEALS, TARGET
journal title
JOURNAL OF BIOLOGICAL CHEMISTRY
J. Biol. Chem.
volume
292
issue
6
pages
2226 - 2236
Web of Science type
Article
Web of Science id
000395530300016
ISSN
0021-9258
1083-351X
DOI
10.1074/jbc.m116.748806
language
English
UGent publication?
yes
classification
A1
additional info
the first two authors contributed equally to this work
copyright statement
I have transferred the copyright for this publication to the publisher
id
8512265
handle
http://hdl.handle.net/1854/LU-8512265
date created
2017-03-02 14:00:24
date last changed
2017-11-13 08:30:23
@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},
}

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.