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Sci Rep. 2016 Nov 16;6:37258. doi: 10.1038/srep37258.

Regulation of Ebola virus VP40 matrix protein by SUMO.

Author information

1
Centro de Investigación en Medicina Molecular (CIMUS), Universidade de Santiago de Compostela, Instituto de Investigaciones Sanitarias (IDIS), Santiago de Compostela, E15706, Spain.
2
Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Martinistraβe 52, D20251, Hamburg, Germany.
3
Bernhard Nocht Institute for Tropical Medicine, Bernhard-Nocht Str 74, D20359, Hamburg, Germany.
4
Department of Macromolecular Structures and NanoBioMedicine Initiative, Centro Nacional de Biotecnología-CSIC, Darwin 3, Madrid 28049, Spain.
5
Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología-CSIC, Darwin 3, Madrid 28049, Spain.
6
Ubiquitylation and Cancer Molecular Biology laboratory, Inbiomed, San Sebastian-Donostia, 20009 Gipuzkoa, Spain.
7
Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Complexo Hospitalario Universitario de Santiago de Compostela (CHUS), SERGAS, Santiago de Compostela, E15706, Spain.
8
Advanced Technology Institute in Life Sciences (ITAV) CNRS-USR3505, 31106 Toulouse, France.
9
University of Toulouse III-Paul Sabatier, 31077, Toulouse, France.

Abstract

The matrix protein of Ebola virus (EBOV) VP40 regulates viral budding, nucleocapsid recruitment, virus structure and stability, viral genome replication and transcription, and has an intrinsic ability to form virus-like particles. The elucidation of the regulation of VP40 functions is essential to identify mechanisms to inhibit viral replication and spread. Post-translational modifications of proteins with ubiquitin-like family members are common mechanisms for the regulation of host and virus multifunctional proteins. Thus far, no SUMOylation of VP40 has been described. Here we demonstrate that VP40 is modified by SUMO and that SUMO is included into the viral like particles (VLPs). We demonstrate that lysine residue 326 in VP40 is involved in SUMOylation, and by analyzing a mutant in this residue we show that SUMO conjugation regulates the stability of VP40 and the incorporation of SUMO into the VLPs. Our study indicates for the first time, to the best of our knowledge, that EBOV hijacks the cellular SUMOylation system in order to modify its own proteins. Modulation of the VP40-SUMO interaction may represent a novel target for the therapy of Ebola virus infection.

PMID:
27849047
PMCID:
PMC5110971
DOI:
10.1038/srep37258
[Indexed for MEDLINE]
Free PMC Article

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