A fatty acid-ordered plasma membrane environment is critical for Ebola virus matrix protein assembly and budding
Plasma membrane (PM) domains and order phases have been shown to play a key role in the assembly, release, and entry of several lipid-enveloped viruses. In the present study, we provide a mechanistic understanding of the Ebola virus (EBOV) matrix protein VP40 interaction with PM lipids and their eff...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-11-01
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| Series: | Journal of Lipid Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227524001688 |
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| author | Souad Amiar Kristen A. Johnson Monica L. Husby Andrea Marzi Robert V. Stahelin |
| author_facet | Souad Amiar Kristen A. Johnson Monica L. Husby Andrea Marzi Robert V. Stahelin |
| author_sort | Souad Amiar |
| collection | DOAJ |
| description | Plasma membrane (PM) domains and order phases have been shown to play a key role in the assembly, release, and entry of several lipid-enveloped viruses. In the present study, we provide a mechanistic understanding of the Ebola virus (EBOV) matrix protein VP40 interaction with PM lipids and their effect on VP40 oligomerization, a crucial step for viral assembly and budding. VP40 matrix formation is sufficient to induce changes in the PM fluidity. We demonstrate that the distance between the lipid headgroups, the fatty acid tail saturation, and the PM order are important factors for the stability of VP40 binding and oligomerization at the PM. The use of FDA-approved drugs to fluidize the PM destabilizes the viral matrix assembly leading to a reduction in budding efficiency. Overall, these findings support an EBOV assembly mechanism that reaches beyond lipid headgroup specificity by using ordered PM lipid regions independent of cholesterol. |
| format | Article |
| id | doaj-art-4e984c7d200344eaad048843b83c8e07 |
| institution | OA Journals |
| issn | 0022-2275 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj-art-4e984c7d200344eaad048843b83c8e072025-08-20T01:54:14ZengElsevierJournal of Lipid Research0022-22752024-11-01651110066310.1016/j.jlr.2024.100663A fatty acid-ordered plasma membrane environment is critical for Ebola virus matrix protein assembly and buddingSouad Amiar0Kristen A. Johnson1Monica L. Husby2Andrea Marzi3Robert V. Stahelin4Borch Department of Medicinal Chemistry & Molecular Pharmacology, Purdue University, West Lafayette, IN; Purdue Institute of Inflammation, Immunology, and Infectious Disease (PI4D), Purdue University, West Lafayette, INDepartment of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, INBorch Department of Medicinal Chemistry & Molecular Pharmacology, Purdue University, West Lafayette, INLaboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MTBorch Department of Medicinal Chemistry & Molecular Pharmacology, Purdue University, West Lafayette, IN; Purdue Institute of Inflammation, Immunology, and Infectious Disease (PI4D), Purdue University, West Lafayette, IN; For correspondence: Robert V. StahelinPlasma membrane (PM) domains and order phases have been shown to play a key role in the assembly, release, and entry of several lipid-enveloped viruses. In the present study, we provide a mechanistic understanding of the Ebola virus (EBOV) matrix protein VP40 interaction with PM lipids and their effect on VP40 oligomerization, a crucial step for viral assembly and budding. VP40 matrix formation is sufficient to induce changes in the PM fluidity. We demonstrate that the distance between the lipid headgroups, the fatty acid tail saturation, and the PM order are important factors for the stability of VP40 binding and oligomerization at the PM. The use of FDA-approved drugs to fluidize the PM destabilizes the viral matrix assembly leading to a reduction in budding efficiency. Overall, these findings support an EBOV assembly mechanism that reaches beyond lipid headgroup specificity by using ordered PM lipid regions independent of cholesterol.http://www.sciencedirect.com/science/article/pii/S0022227524001688Ebola viruslipid acyl chainsmembrane fluidityphosphatidylserineplasma membranevirus assembly |
| spellingShingle | Souad Amiar Kristen A. Johnson Monica L. Husby Andrea Marzi Robert V. Stahelin A fatty acid-ordered plasma membrane environment is critical for Ebola virus matrix protein assembly and budding Journal of Lipid Research Ebola virus lipid acyl chains membrane fluidity phosphatidylserine plasma membrane virus assembly |
| title | A fatty acid-ordered plasma membrane environment is critical for Ebola virus matrix protein assembly and budding |
| title_full | A fatty acid-ordered plasma membrane environment is critical for Ebola virus matrix protein assembly and budding |
| title_fullStr | A fatty acid-ordered plasma membrane environment is critical for Ebola virus matrix protein assembly and budding |
| title_full_unstemmed | A fatty acid-ordered plasma membrane environment is critical for Ebola virus matrix protein assembly and budding |
| title_short | A fatty acid-ordered plasma membrane environment is critical for Ebola virus matrix protein assembly and budding |
| title_sort | fatty acid ordered plasma membrane environment is critical for ebola virus matrix protein assembly and budding |
| topic | Ebola virus lipid acyl chains membrane fluidity phosphatidylserine plasma membrane virus assembly |
| url | http://www.sciencedirect.com/science/article/pii/S0022227524001688 |
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