Affiliation:
1. Institut für Virologie, Philipps-Universität Marburg, Marburg, Germany
2. Laboratory of Ultrastructural Virology, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan
3. German Center of Infection Research (DZIF), Partner Site Giessen-Marburg-Langen, Marburg, Germany
4. Protein Analytics, Faculty of Biology, Philipps University Marburg, Marburg, Germany
Abstract
The largest Ebola virus (EBOV) epidemic in West Africa ever caused more than 28,000 cases and 11,000 deaths, and the current EBOV epidemic in the Democratic Republic of the Congo continues, with more than 3,000 cases to date. Therefore, it is essential to develop antivirals against EBOV. Recently, an inhibitor of the cellular phosphatase PP2A-mediated dephosphorylation of the EBOV transcription factor VP30 has been shown to suppress the spread of Ebola virus. Here, we identified the protein kinase SRPK1 as a VP30-specific kinase that phosphorylates serine 29, the same residue that is dephosphorylated by PP2A. SRPK1-mediated phosphorylation of serine 29 enabled primary viral transcription. Mutation of the SRPK1 recognition motif in VP30 resulted in significant growth inhibition of EBOV. Similarly, elevation of the phosphorylation status of serine 29 by overexpression of SRPK1 inhibited EBOV growth, highlighting the importance of reversible phosphorylation of VP30 as a potential therapeutic target.
Funder
TERUMO LIFE SCIENCE FOUNDATION
Deutsche Forschungsgemeinschaft
Takeda Science Foundation
Daiichi Sankyo Foundation of Life Science
Uehara Memorial Foundation
Japan Agency for Medical Research and Development
University of Tokyo
MEXT | Japan Society for the Promotion of Science
Japan Research Foundation for Clinical Pharmacology
Kyoto University
MSD Life Science Foundation, Public Interest Incorporated Foundation
the German Center for Infection Research, Emerging Infections
Publisher
American Society for Microbiology
Cited by
29 articles.
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