Regulation of Ebola virus VP40 matrix protein by SUMO.
Maite Baz-Martínez, Ahmed El Motiam, Paula Ruibal, Gabriela N Condezo, Carlos F de la Cruz-Herrera, Valerie Lang, Manuel Collado, Carmen San Martín, Manuel S Rodríguez, Cesar Muñoz-Fontela, Carmen Rivas
Author Information
Maite Baz-Martínez: Centro de Investigación en Medicina Molecular (CIMUS), Universidade de Santiago de Compostela, Instituto de Investigaciones Sanitarias (IDIS), Santiago de Compostela, E15706, Spain.
Ahmed El Motiam: Centro de Investigación en Medicina Molecular (CIMUS), Universidade de Santiago de Compostela, Instituto de Investigaciones Sanitarias (IDIS), Santiago de Compostela, E15706, Spain.
Paula Ruibal: Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Martinistraβe 52, D20251, Hamburg, Germany.
Gabriela N Condezo: Department of Macromolecular Structures and NanoBioMedicine Initiative, Centro Nacional de Biotecnología-CSIC, Darwin 3, Madrid 28049, Spain.
Carlos F de la Cruz-Herrera: Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología-CSIC, Darwin 3, Madrid 28049, Spain.
Valerie Lang: Ubiquitylation and Cancer Molecular Biology laboratory, Inbiomed, San Sebastian-Donostia, 20009 Gipuzkoa, Spain.
Manuel Collado: Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Complexo Hospitalario Universitario de Santiago de Compostela (CHUS), SERGAS, Santiago de Compostela, E15706, Spain.
Carmen San Martín: Department of Macromolecular Structures and NanoBioMedicine Initiative, Centro Nacional de Biotecnología-CSIC, Darwin 3, Madrid 28049, Spain.
Manuel S Rodríguez: Advanced Technology Institute in Life Sciences (ITAV) CNRS-USR3505, 31106 Toulouse, France.
Cesar Muñoz-Fontela: Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Martinistraβe 52, D20251, Hamburg, Germany.
Carmen Rivas: Centro de Investigación en Medicina Molecular (CIMUS), Universidade de Santiago de Compostela, Instituto de Investigaciones Sanitarias (IDIS), Santiago de Compostela, E15706, Spain.
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.
References
Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):15936-41
[PMID: 14673115]
