title: Regulation of Ebola virus VP40 matrix protein by SUMO.
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.
authors.affiliation: Centro de Investigación en Medicina Molecular (CIMUS), Universidade de Santiago de Compostela, Instituto de Investigaciones Sanitarias (IDIS), Santiago de Compostela, E15706, Spain.
authors.forename: Maite
authors.initials: M
authors.lastname: Baz-Martínez
authors.affiliation: Centro de Investigación en Medicina Molecular (CIMUS), Universidade de Santiago de Compostela, Instituto de Investigaciones Sanitarias (IDIS), Santiago de Compostela, E15706, Spain.
authors.forename: Ahmed
authors.initials: A
authors.lastname: El Motiam
authors.affiliation: Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Martinistraβe 52, D20251, Hamburg, Germany.|Bernhard Nocht Institute for Tropical Medicine, Bernhard-Nocht Str 74, D20359, Hamburg, Germany.
authors.forename: Paula
authors.initials: P
authors.lastname: Ruibal
authors.affiliation: Department of Macromolecular Structures and NanoBioMedicine Initiative, Centro Nacional de Biotecnología-CSIC, Darwin 3, Madrid 28049, Spain.
authors.forename: Gabriela N
authors.initials: GN
authors.lastname: Condezo
authors.affiliation: Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología-CSIC, Darwin 3, Madrid 28049, Spain.
authors.forename: Carlos F
authors.initials: CF
authors.lastname: de la Cruz-Herrera
authors.affiliation: Ubiquitylation and Cancer Molecular Biology laboratory, Inbiomed, San Sebastian-Donostia, 20009 Gipuzkoa, Spain.
authors.forename: Valerie
authors.initials: V
authors.lastname: Lang
authors.affiliation: Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Complexo Hospitalario Universitario de Santiago de Compostela (CHUS), SERGAS, Santiago de Compostela, E15706, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Collado
authors.affiliation: Department of Macromolecular Structures and NanoBioMedicine Initiative, Centro Nacional de Biotecnología-CSIC, Darwin 3, Madrid 28049, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: San Martín
authors.affiliation: Advanced Technology Institute in Life Sciences (ITAV) CNRS-USR3505, 31106 Toulouse, France.|University of Toulouse III-Paul Sabatier, 31077, Toulouse, France.
authors.forename: Manuel S
authors.initials: MS
authors.lastname: Rodríguez
authors.affiliation: Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Martinistraβe 52, D20251, Hamburg, Germany.|Bernhard Nocht Institute for Tropical Medicine, Bernhard-Nocht Str 74, D20359, Hamburg, Germany.
authors.forename: Cesar
authors.initials: C
authors.lastname: Muñoz-Fontela
authors.affiliation: Centro de Investigación en Medicina Molecular (CIMUS), Universidade de Santiago de Compostela, Instituto de Investigaciones Sanitarias (IDIS), Santiago de Compostela, E15706, Spain.|Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología-CSIC, Darwin 3, Madrid 28049, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Rivas
mesh_terms: D000818:Animals; D002522:Chlorocebus aethiops; D029043:Ebolavirus / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D019142:Hemorrhagic Fever, Ebola / Q000821:virology; D054884:Host-Pathogen Interactions; D006801:Humans; D008239:Lysine / Q000235:genetics / Q000378:metabolism*; D008854:Microscopy, Electron; D009154:Mutation; D009698:Nucleoproteins / Q000235:genetics / Q000378:metabolism*; D058207:Sumoylation; D014709:Vero Cells; D014758:Viral Core Proteins / Q000235:genetics / Q000378:metabolism*; D014771:Virion / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D009698:Nucleoproteins; D014758:Viral Core Proteins; C084819:nucleoprotein VP40, Ebola virus; D008239:Lysine