scholarly journals Conformational plasticity of the Ebola virus matrix protein

2014 ◽  
Vol 23 (11) ◽  
pp. 1519-1527 ◽  
Author(s):  
Jens Radzimanowski ◽  
Gregory Effantin ◽  
Winfried Weissenhorn
Keyword(s):  
Matrix Protein ◽  
Ebola Virus ◽  
Conformational Plasticity

Structure and functions of the Ebola virus matrix protein VP40

2019 ◽  
Vol 14 (1) ◽  
pp. 21-30
Author(s):  
Janine Brandt ◽  
Lisa Wendt ◽  
Thomas Hoenen
Keyword(s):  
Matrix Protein ◽  
Ebola Virus ◽  
Structure And Functions

scholarly journals Exploiting the Reverse Vaccinology Approach to Design Novel Subunit Vaccine against Ebola Virus

2020 ◽  
Author(s):  
Md. Asad Ullah ◽  
Bishajit Sarkar ◽  
Syed Sajidul Islam
Keyword(s):  
Molecular Docking ◽  
Mhc Class Ii ◽  
Large Scale ◽  
Matrix Protein ◽  
Ebola Virus ◽  
Rna Virus ◽  
Docking Study ◽  
Dynamics Simulation ◽  
Molecular Docking Study ◽  
Class I Mhc

AbstractEbola virus is a highly pathogenic RNA virus that causes haemorrhagic fever in human. With very high mortality rate, Ebola virus is considered as one of the dangerous viruses in the world. Although, the Ebola outbreaks claimed many lives in the past, no satisfactory treatment or vaccine have been discovered yet to fight against Ebola. For this reason, in this study, various tools of bioinformatics and immunoinformatics were used to design possible vaccines against Zaire Ebola virus strain Mayinga-76. To construct the vaccine, three potential antigenic proteins of the virus, matrix protein VP40, envelope glycoprotein and nucleoprotein were selected against which the vaccines would be designed. The MHC class-I, MHC class-II and B-cell epitopes were determined and after robust analysis through various tools and molecular docking analysis, three vaccine candidates, designated as EV-1, EV-2 and EV-3, were constructed. Since the highly conserved epitopes were used for vaccine construction, these vaccine constructs are also expected to be effective on other strains of Ebola virus like strain Gabon-94 and Kikwit-95. Next, the molecular docking study on these vaccine constructs were analyzed by molecular docking study and EV-1 emerged as the best vaccine construct. Later, molecular dynamics simulation study revealed the good performances as well as good stability of the vaccine protein. Finally, codon adaptation and in silico cloning were conducted to design a possible plasmid (pET-19b plasmid vector was used) for large scale, industrial production of the EV-1 vaccine.

Proximity proteomics identifies novel function of Rab14 in trafficking of Ebola virus matrix protein VP40

2020 ◽  
Vol 527 (2) ◽  
pp. 387-392
Author(s):  
Jiannan Fan ◽  
Xuechun Liu ◽  
Feifei Mao ◽  
Xihua Yue ◽  
Intaek Lee ◽  
...  
Keyword(s):  
Matrix Protein ◽  
Ebola Virus

scholarly journals Quantitative serology assays for determination of antibody responses to Ebola virus glycoprotein and matrix protein in nonhuman primates and humans

2016 ◽  
Vol 126 ◽  
pp. 55-61 ◽  
Author(s):  
Hong Vu ◽  
Sergey Shulenin ◽  
Allen Grolla ◽  
Jonathan Audet ◽  
Shihua He ◽  
...  
Keyword(s):  
Nonhuman Primates ◽  
Matrix Protein ◽  
Ebola Virus ◽  
Antibody Responses ◽  
Virus Glycoprotein

scholarly journals Host Cell Plasma Membrane Phosphatidylserine Regulates the Assembly and Budding of Ebola Virus

2015 ◽  
Vol 89 (18) ◽  
pp. 9440-9453 ◽  
Author(s):  
Emmanuel Adu-Gyamfi ◽  
Kristen A. Johnson ◽  
Mark E. Fraser ◽  
Jordan L. Scott ◽  
Smita P. Soni ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Host Cell ◽  
Human Cell ◽  
Mammalian Cells ◽  
Matrix Protein ◽  
Ebola Virus ◽  
Cell Plasma Membrane ◽  
Replication Process ◽  
Cell Plasma

ABSTRACTLipid-enveloped viruses replicate and bud from the host cell where they acquire their lipid coat. Ebola virus, which buds from the plasma membrane of the host cell, causes viral hemorrhagic fever and has a high fatality rate. To date, little has been known about how budding and egress of Ebola virus are mediated at the plasma membrane. We have found that the lipid phosphatidylserine (PS) regulates the assembly of Ebola virus matrix protein VP40. VP40 binds PS-containing membranes with nanomolar affinity, and binding of PS regulates VP40 localization and oligomerization on the plasma membrane inner leaflet. Further, alteration of PS levels in mammalian cells inhibits assembly and egress of VP40. Notably, interactions of VP40 with the plasma membrane induced exposure of PS on the outer leaflet of the plasma membrane at sites of egress, whereas PS is typically found only on the inner leaflet. Taking the data together, we present a model accounting for the role of plasma membrane PS in assembly of Ebola virus-like particles.IMPORTANCEThe lipid-enveloped Ebola virus causes severe infection with a high mortality rate and currently lacks FDA-approved therapeutics or vaccines. Ebola virus harbors just seven genes in its genome, and there is a critical requirement for acquisition of its lipid envelope from the plasma membrane of the human cell that it infects during the replication process. There is, however, a dearth of information available on the required contents of this envelope for egress and subsequent attachment and entry. Here we demonstrate that plasma membrane phosphatidylserine is critical for Ebola virus budding from the host cell plasma membrane. This report, to our knowledge, is the first to highlight the role of lipids in human cell membranes in the Ebola virus replication cycle and draws a clear link between selective binding and transport of a lipid across the membrane of the human cell and use of that lipid for subsequent viral entry.

scholarly journals Regulation of the Ebola Virus VP24 Protein by SUMO

2019 ◽  
Vol 94 (1) ◽  
Author(s):  
Santiago Vidal ◽  
Ahmed El Motiam ◽  
Rocío Seoane ◽  
Viktorija Preitakaite ◽  
Yanis Hichem Bouzaher ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Viral Protein ◽  
Matrix Protein ◽  
Ebola Virus ◽  
Nuclear Translocation ◽  
Critical Role ◽  
Innate Immune ◽  
Type I ◽  
Negative Modulator

ABSTRACT Some viruses take advantage of conjugation of ubiquitin or ubiquitin-like proteins to enhance their own replication. One example is Ebola virus, which has evolved strategies to utilize these modification pathways to regulate the viral proteins VP40 and VP35 and to counteract the host defenses. Here, we show a novel mechanism by which Ebola virus exploits the ubiquitin and SUMO pathways. Our data reveal that minor matrix protein VP24 of Ebola virus is a bona fide SUMO target. Analysis of a SUMOylation-defective VP24 mutant revealed a reduced ability to block the type I interferon (IFN) pathway and to inhibit IFN-mediated STAT1 nuclear translocation, exhibiting a weaker interaction with karyopherin 5 and significantly diminished stability. Using glutathione S-transferase (GST) pulldown assay, we found that VP24 also interacts with SUMO in a noncovalent manner through a SIM domain. Mutation of the SIM domain in VP24 resulted in a complete inability of the protein to downmodulate the IFN pathway and in the monoubiquitination of the protein. We identified SUMO deubiquitinating enzyme ubiquitin-specific-processing protease 7 (USP7) as an interactor and a negative modulator of VP24 ubiquitination. Finally, we show that mutation of one ubiquitination site in VP24 potentiates the IFN modulatory activity of the viral protein and its ability to block IFN-mediated STAT1 nuclear translocation, pointing to the ubiquitination of VP24 as a negative modulator of the VP24 activity. Altogether, these results indicate that SUMO interacts with VP24 and promotes its USP7-mediated deubiquitination, playing a key role in the interference with the innate immune response mediated by the viral protein. IMPORTANCE The Ebola virus VP24 protein plays a critical role in escape of the virus from the host innate immune response. Therefore, deciphering the molecular mechanisms modulating VP24 activity may be useful to identify potential targets amenable to therapeutics. Here, we identify the cellular proteins USP7, SUMO, and ubiquitin as novel interactors and regulators of VP24. These interactions may represent novel potential targets to design new antivirals with the ability to modulate Ebola virus replication.

scholarly journals Ebola Virus VP35-VP40 Interaction Is Sufficient for Packaging 3E-5E Minigenome RNA into Virus-Like Particles

2006 ◽  
Vol 80 (11) ◽  
pp. 5135-5144 ◽  
Author(s):  
Reed F. Johnson ◽  
Sarah E. McCarthy ◽  
Peter J. Godlewski ◽  
Ronald N. Harty
Keyword(s):  
Confocal Microscopy ◽  
Reverse Transcriptase ◽  
Matrix Protein ◽  
Ebola Virus ◽  
Genomic Rna ◽  
Transfected Cells ◽  
Virus Like Particles ◽  
Rna Complexes ◽  
Viral Genomic Rna ◽  
Two Hybrid

ABSTRACT The packaging of viral genomic RNA into nucleocapsids and subsequently into virions is not completely understood. Phosphoprotein (P) and nucleoprotein (NP) interactions link NP-RNA complexes with P-L (polymerase) complexes to form viral nucleocapsids. The nucleocapsid then interacts with the viral matrix protein, leading to specific packaging of the nucleocapsid into the virion. A mammalian two-hybrid assay and confocal microscopy were used to demonstrate that Ebola virus VP35 and VP40 interact and colocalize in transfected cells. VP35 was packaged into budding virus-like particles (VLPs) as observed by protease protection assays. Moreover, VP40 and VP35 were sufficient for packaging an Ebola virus minignome RNA into VLPs. Results from immunoprecipitation-reverse transcriptase PCR experiments suggest that VP35 confers specificity of the nucleocapsid for viral genomic RNA by direct VP35-RNA interactions.

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