Ebolavirus VP24 binding to karyopherins is required for inhibition of interferon signaling.
The Ebolavirus VP24 protein counteracts alpha/beta interferon (IFN-alpha/beta) and IFN-gamma signaling by blocking the nuclear accumulation of tyrosine-phosphorylated STAT1 (PY-STAT1). According to the proposed model, VP24 binding to members of the NPI-1 subfamily of karyopherin alpha (KPNalpha) nuclear localization signal receptors prevents their binding to PY-STAT1, thereby preventing PY-STAT1 nuclear accumulation. This study now identifies two domains of VP24 required for inhibition of IFN-beta-induced gene expression and PY-STAT1 nuclear accumulation. We demonstrate that loss of function correlates with loss of binding to KPNalpha proteins. Thus, the VP24 IFN antagonist function requires the ability of VP24 to interact with KPNalpha.
Mateo
Mathieu
M
Laboratoire des Filovirus, INSERM U758, University Claude Bernard Lyon-1, 21 Av. Tony Garnier, 69365 Lyon Cedex 07, France.
Reid
St Patrick
SP
Leung
Lawrence W
LW
Basler
Christopher F
CF
Volchkov
Viktor E
VE
D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002522:Chlorocebus aethiops; D029043:Ebolavirus / Q000378:metabolism*; D006801:Humans; D016899:Interferon-beta / Q000235:genetics / Q000378:metabolism; D007372:Interferons / Q000187:drug effects / Q000378:metabolism*; D009154:Mutation; D010766:Phosphorylation; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014709:Vero Cells; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D028901:alpha Karyopherins / Q000235:genetics / Q000378:metabolism*
D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; C446938:VP24 protein, Ebola virus; D014764:Viral Proteins; D028901:alpha Karyopherins; D016899:Interferon-beta; D007372:Interferons