Antagonism of STAT3 signalling by Ebola virus

Angela R. Harrison, Shawn Todd, Megan Dearnley, Cassandra T. David, Diane Green, Stephen M. Rawlinson, Gough G. Au, Glenn A. Marsh, Gregory W. Moseley (Lead / Corresponding author)

    Research output: Contribution to journalArticlepeer-review

    6 Citations (Scopus)
    28 Downloads (Pure)

    Abstract

    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.

    Original languageEnglish
    Article numbere1009636
    Number of pages21
    JournalPLoS Pathogens
    Volume17
    Issue number6
    DOIs
    Publication statusPublished - 24 Jun 2021

    Keywords

    • Animals
    • Chlorocebus aethiops
    • Ebolavirus
    • HEK293 Cells
    • Hemorrhagic Fever, Ebola/metabolism
    • Humans
    • STAT3 Transcription Factor/antagonists & inhibitors
    • Signal Transduction/physiology
    • Vero Cells
    • Viral Proteins/metabolism

    Fingerprint

    Dive into the research topics of 'Antagonism of STAT3 signalling by Ebola virus'. Together they form a unique fingerprint.

    Cite this