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Antagonism of STAT3 signalling by Ebola virus

by Rawlinson, Stephen M. , Dearnley, Megan , Au, Gough G. , Marsh, Glenn A. , Todd, Shawn , David, Cassandra T. , Moseley, Gregory W. , Harrison, Angela R. , Green, Diane

in Antagonism / Antiviral drugs / Binding sites / Biology and life sciences / Cellular signal transduction / Cytokines / Ebola virus / Ebolavirus / Epidemics / Fatalities / Genetic aspects / Health aspects / Hemorrhagic fever / Host-virus relationships / Immune response / Infections / Interferon / Interleukin / Interleukin 6 / Localization / Medicine and Health Sciences / Molecular modelling / Proteins / Rabies / Research and Analysis Methods / Signaling / Stat1 protein / Stat3 protein / Statistical analysis / Transcription factors / Transducers / Viral diseases / Viral infections / Viruses / VP24 protein

2021

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Antagonism of STAT3 signalling by Ebola virus

by Rawlinson, Stephen M. , Dearnley, Megan , Au, Gough G. , Marsh, Glenn A. , Todd, Shawn , David, Cassandra T. , Moseley, Gregory W. , Harrison, Angela R. , Green, Diane

2021

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Antagonism of STAT3 signalling by Ebola virus

by Rawlinson, Stephen M. , Dearnley, Megan , Au, Gough G. , Marsh, Glenn A. , Todd, Shawn , David, Cassandra T. , Moseley, Gregory W. , Harrison, Angela R. , Green, Diane

2021

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Journal Article

Antagonism of STAT3 signalling by Ebola virus

Rawlinson, Stephen M.,

Dearnley, Megan,

Au, Gough G.,

Marsh, Glenn A.,

Todd, Shawn,

David, Cassandra T.,

Moseley, Gregory W.,

Harrison, Angela R.,

Green, Diane

2021

Overview

Many viruses target signal transducers and activators of transcription (STAT) 1 and 2 to antagonise antiviral interferon signalling, but targeting of signalling by other STATs/cytokines, including STAT3/interleukin 6 that regulate processes important to Ebola virus (EBOV) haemorrhagic fever, is poorly defined. We report that EBOV potently inhibits STAT3 responses to interleukin-6 family cytokines, and that this is mediated by the interferon-antagonist VP24. Mechanistic analysis indicates that VP24 effects a unique strategy combining distinct karyopherin-dependent and karyopherin-independent mechanisms to antagonise STAT3-STAT1 heterodimers and STAT3 homodimers, respectively. This appears to reflect distinct mechanisms of nuclear trafficking of the STAT3 complexes, revealed for the first time by our analysis of VP24 function. These findings are consistent with major roles for global inhibition of STAT3 signalling in EBOV infection, and provide new insights into the molecular mechanisms of STAT3 nuclear trafficking, significant to pathogen-host interactions, cell physiology and pathologies such as cancer.

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Publisher

Public Library of Science,Public Library of Science (PLoS)

Subject

Antagonism

/ Antiviral drugs

/ Binding sites

/ Biology and life sciences

/ Cellular signal transduction

/ Cytokines

/ Ebola virus