JVI Accepts, published online ahead of print on 4 November 2009

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J. Virol. doi:10.1128/JVI.01372-09
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Ebolavirus VP24 binding to karyopherins is required for inhibition of interferon signalling.

Mathieu Mateo, St Patrick Reid, Lawrence W. Leung, Christopher F. Basler^*, and Viktor E. Volchkov^*

Laboratoire des Filovirus, Inserm U758, 21 av. Tony Garnier, Lyon, F-69007, France; Université de Lyon, Lyon, F-69007, France; Université Lyon 1, Villeurbanne F-69622, France; IFR 128 BioSciences Gerland-Lyon Sud, Lyon, F-69007, France; Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029

^* To whom correspondence should be addressed. Email: chris.basler{at}mssm.edu. viktor.volchkov{at}inserm.fr.

The ebolavirus VP24 protein counteracts interferon (IFN)-/ and IFN signalling 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 (KPN) 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--induced gene expression and PY-STAT1 nuclear accumulation. We demonstrate that loss-of-function correlates with loss of binding to KPNs. Thus, VP24 IFN-antagonist function requires its ability to interact with KPN.