دورية أكاديمية
أعرض في EDS

Phosphatidylserine clustering by the Ebola virus matrix protein is a critical step in viral budding.

التفاصيل البيبلوغرافية
العنوان: Phosphatidylserine clustering by the Ebola virus matrix protein is a critical step in viral budding.
المؤلفون: Husby ML; Department of Medicinal Chemistry & Molecular Pharmacology, Purdue University, West Lafayette, IN, USA.; Purdue Institute of Inflammation, Immunology and Infectious Disease (PI4D), Purdue University, West Lafayette, West Lafayette, IN, USA., Amiar S; Department of Medicinal Chemistry & Molecular Pharmacology, Purdue University, West Lafayette, IN, USA.; Purdue Institute of Inflammation, Immunology and Infectious Disease (PI4D), Purdue University, West Lafayette, West Lafayette, IN, USA., Prugar LI; United States Army Medical Research Institute of Infectious Diseases USAMRIID, Fort Detrick, Frederick, MD, USA., David EA; Department of Medicinal Chemistry & Molecular Pharmacology, Purdue University, West Lafayette, IN, USA., Plescia CB; Department of Medicinal Chemistry & Molecular Pharmacology, Purdue University, West Lafayette, IN, USA., Huie KE; United States Army Medical Research Institute of Infectious Diseases USAMRIID, Fort Detrick, Frederick, MD, USA., Brannan JM; United States Army Medical Research Institute of Infectious Diseases USAMRIID, Fort Detrick, Frederick, MD, USA., Dye JM; United States Army Medical Research Institute of Infectious Diseases USAMRIID, Fort Detrick, Frederick, MD, USA., Pienaar E; Purdue Institute of Inflammation, Immunology and Infectious Disease (PI4D), Purdue University, West Lafayette, West Lafayette, IN, USA.; Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, USA., Stahelin RV; Department of Medicinal Chemistry & Molecular Pharmacology, Purdue University, West Lafayette, IN, USA.; Purdue Institute of Inflammation, Immunology and Infectious Disease (PI4D), Purdue University, West Lafayette, West Lafayette, IN, USA.
المصدر: EMBO reports [EMBO Rep] 2022 Nov 07; Vol. 23 (11), pp. e51709. Date of Electronic Publication: 2022 Sep 12.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 100963049 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1469-3178 (Electronic) Linking ISSN: 1469221X NLM ISO Abbreviation: EMBO Rep Subsets: MEDLINE
أسماء مطبوعة: Publication: 2024- : [London] : Nature Publishing Group
Original Publication: Oxford, UK : Published for EMBO by Oxford University Press, 2000-
مواضيع طبية MeSH: Hemorrhagic Fever, Ebola*/metabolism , Ebolavirus*/physiology, Animals ; Phosphatidylserines/metabolism ; Fendiline/metabolism ; Viral Matrix Proteins/metabolism ; Virus Assembly ; Cluster Analysis ; Mammals/metabolism
مستخلص: Phosphatidylserine (PS) is a critical lipid factor in the assembly and spread of numerous lipid-enveloped viruses. Here, we describe the ability of the Ebola virus (EBOV) matrix protein eVP40 to induce clustering of PS and promote viral budding in vitro, as well as the ability of an FDA-approved drug, fendiline, to reduce PS clustering and subsequent virus budding and entry. To gain mechanistic insight into fendiline inhibition of EBOV replication, multiple in vitro assays were run including imaging, viral budding and viral entry assays. Fendiline lowers PS content in mammalian cells and PS in the plasma membrane, where the ability of VP40 to form new virus particles is greatly lower. Further, particles that form from fendiline-treated cells have altered particle morphology and cannot significantly infect/enter cells. These complementary studies reveal the mechanism by which EBOV matrix protein clusters PS to enhance viral assembly, budding, and spread from the host cell while also laying the groundwork for fundamental drug targeting strategies.
(© 2022 The Authors. Published under the terms of the CC BY NC ND 4.0 license.)
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معلومات مُعتمدة: T32 GM075762 United States GM NIGMS NIH HHS; R01 AI081077 United States AI NIAID NIH HHS; UL1 TR001108 United States TR NCATS NIH HHS; T32 GM132024 United States GM NIGMS NIH HHS; T32 AI148103 United States AI NIAID NIH HHS
فهرسة مساهمة: Keywords: Ebola virus; matrix protein; phosphatidylserine; plasma membrane; viral budding
المشرفين على المادة: 0 (Phosphatidylserines)
S253D559A8 (Fendiline)
0 (Viral Matrix Proteins)
تواريخ الأحداث: Date Created: 20220912 Date Completed: 20221108 Latest Revision: 20230519
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC9638875
DOI: 10.15252/embr.202051709
PMID: 36094794
قاعدة البيانات: MEDLINE
الوصف
تدمد:1469-3178
DOI:10.15252/embr.202051709