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

TY - JOUR

T1 - The Ebola Virus Nucleoprotein Recruits the Host PP2A-B56 Phosphatase to Activate Transcriptional Support Activity of VP30

AU - Kruse, Thomas

AU - Biedenkopf, Nadine

AU - Hertz, Emil Peter Thrane

AU - Dietzel, Erik

AU - Stalmann, Gertrud

AU - López-Méndez, Blanca

AU - Davey, Norman E

AU - Nilsson, Jakob

AU - Becker, Stephan

N1 - Copyright © 2017 Elsevier Inc. All rights reserved.

PY - 2018/1/4

Y1 - 2018/1/4

N2 - 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.

AB - 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.

U2 - 10.1016/j.molcel.2017.11.034

DO - 10.1016/j.molcel.2017.11.034

M3 - Journal article

C2 - 29290611

SN - 1097-2765

VL - 69

SP - 136

EP - 145

JO - Molecular Cell

JF - Molecular Cell

IS - 1

ER -