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Mol Cell. 2018 Jan 4;69(1):136-145.e6. doi: 10.1016/j.molcel.2017.11.034. Epub 2017 Dec 28.

The Ebola Virus Nucleoprotein Recruits the Host PP2A-B56 Phosphatase to Activate Transcriptional Support Activity of VP30.

Author information

1
The Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark.
2
Institute of Virology, Philipps Universität Marburg, Marburg, Germany; German Center of Infection Research (DZIF), Giessen-Marburg-Langen, Marburg, Germany.
3
Conway Institute of Biomolecular and Biomedical Sciences, University College Dublin, Dublin 4, Ireland.
4
The Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark. Electronic address: jakob.nilsson@cpr.ku.dk.
5
Institute of Virology, Philipps Universität Marburg, Marburg, Germany; German Center of Infection Research (DZIF), Giessen-Marburg-Langen, Marburg, Germany. Electronic address: becker@staff.uni-marburg.de.

Abstract

Transcription of the Ebola virus genome depends on the viral transcription factor VP30 in its unphosphorylated form, but the underlying molecular mechanism of VP30 dephosphorylation is unknown. Here we show that the Ebola virus nucleoprotein (NP) recruits the host PP2A-B56 protein phosphatase through a B56-binding LxxIxE motif and that this motif is essential for VP30 dephosphorylation and viral transcription. The LxxIxE motif and the binding site of VP30 in NP are in close proximity, and both binding sites are required for the dephosphorylation of VP30. We generate a specific inhibitor of PP2A-B56 and show that it suppresses Ebola virus transcription and infection. This work dissects the molecular mechanism of VP30 dephosphorylation by PP2A-B56, and it pinpoints this phosphatase as a potential target for therapeutic intervention.

KEYWORDS:

B56; B’; Ebola virus; LxxIxE; NP; PP2A; VP30; filovirus; nucleoprotein; transcription regulation

PMID:
29290611
DOI:
10.1016/j.molcel.2017.11.034
[Indexed for MEDLINE]
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