A Loop Region in the N-Terminal Domain of Ebola Virus VP40 Is Important in Viral Assembly, Budding, and Egress
| Autor: | Enrico Gratton, Smita P. Soni, Michelle A. Digman, Clara S. Jee, Robert V. Stahelin, Emmanuel Adu-Gyamfi |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
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Molecular filovirus Viral protein Viral budding viruses VP40 lcsh:QR1-502 Biology medicine.disease_cause plasma membrane Article Virus lcsh:Microbiology Cell Line Viral Matrix Proteins 03 medical and health sciences Ebola virus Protein Domains Viral entry Virology medicine Humans viral budding Virus Release 030304 developmental biology 0303 health sciences Viral matrix protein Virus Assembly Cell Membrane 030302 biochemistry & molecular biology Hemorrhagic Fever Ebola Ebolavirus number and brightness analysis 3. Good health Infectious Diseases Mutation Dimerization |
| Zdroj: | Viruses, Vol 6, Iss 10, Pp 3837-3854 (2014) Adu-Gyamfi, E; Soni, SP; Jee, CS; Digman, MA; Gratton, E; & Stahelin, RV. (2014). A loop region in the N-terminal domain of ebola virus VP40 is important in viral assembly, Budding, and egress. Viruses, 6(10), 3837-3854. doi: 10.3390/v6103837. UC Irvine: Retrieved from: http://www.escholarship.org/uc/item/2ps6j95s Viruses Volume 6 Issue 10 Pages 3837-3854 |
| ISSN: | 1999-4915 |
| DOI: | 10.3390/v6103837. |
| Popis: | © 2014 by the authors; licensee MDPI, Basel, Switzerland. Ebola virus (EBOV) causes viral hemorrhagic fever in humans and can have clinical fatality rates of ∼60%. The EBOV genome consists of negative sense RNA that encodes seven proteins including viral protein 40 (VP40). VP40 is the major Ebola virus matrix protein and regulates assembly and egress of infectious Ebola virus particles. It is well established that VP40 assembles on the inner leaflet of the plasma membrane of human cells to regulate viral budding where VP40 can produce virus like particles (VLPs) without other Ebola virus proteins present. The mechanistic details, however, of VP40 lipid-interactions and protein-protein interactions that are important for viral release remain to be elucidated. Here, we mutated a loop region in the N-terminal domain of VP40 (Lys127, Thr129, and Asn130) and find that mutations (K127A, T129A, and N130A) in this loop region reduce plasma membrane localization of VP40. Additionally, using total internal reflection fluorescence microscopy and number and brightness analysis we demonstrate these mutations greatly reduce VP40 oligomerization. Lastly, VLP assays demonstrate these mutations significantly reduce VLP release from cells. Taken together, these studies identify an important loop region in VP40 that may be essential to viral egress. |
| Databáze: | OpenAIRE |
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