Ebola Zaire VP40
Description
Oligomerization-Dependent Roles
VP40 adopts distinct oligomeric states with specialized functions:
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Dimers: Cytoplasmic form stabilized by NTD interactions; essential for intracellular transport .
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Octamers: Perinuclear ring structures that suppress viral RNA synthesis by sequestering transcription-essential factors .
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Hexamers: Plasma membrane-associated filaments serving as scaffolds for virion assembly .
Virion Assembly and Budding
VP40 executes a four-step assembly process:
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Membrane Binding: CTD hydrophobic loops anchor VP40 to the plasma membrane inner leaflet .
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Hexamerization: Linear hexamers form matrix filaments through CTD interactions .
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Host Protein Recruitment:
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VLP Budding: VP40 alone generates filamentous virus-like particles (VLPs) measuring ~65 nm in diameter . Coexpression with glycoprotein (GP) or nucleoprotein (NP) enhances VLP yield by 2–3× .
Host Interaction Network
VP40 exploits multiple host pathways:
VLP Production and Applications
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Autonomous Budding: VP40 expression alone induces 65-nm filamentous VLPs, confirming its sufficiency for particle formation .
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GP/NP Synergy: Coexpression with GP incorporates spike proteins into VLPs, while NP increases budding efficiency by stabilizing VP40 filaments .
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Therapeutic VLPs: VP40-based VLPs elicit protective immunity in murine models, serving as non-infectious vaccine candidates .
Therapeutic Targeting Strategies
VP40’s essential roles make it a prime antiviral target:
Evolutionary and Functional Insights
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Conformational Switching: Host-derived RNA binding triggers VP40 structural changes, enabling phase-specific functions (e.g., transcription suppression vs. budding) .
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Conservation: The PTAP/PPEY motifs and hydrophobic loops are conserved across Ebolavirus species, underscoring their functional necessity .
Future Directions
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Structural Dynamics: Resolve real-time VP40 oligomerization using cryo-ET or single-molecule imaging.
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Host Factor Screens: Identify novel interactors via proximity-dependent biotinylation (BioID).
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Clinical Development: Optimize VP40-targeting inhibitors for pharmacokinetic stability and in vivo efficacy.
Product Specs
Product Science Overview
The Ebola virus (EBOV) is a member of the Filoviridae family, which includes two genera: Ebolavirus and Marburgvirus. The Ebola virus is responsible for causing severe hemorrhagic fever in humans and nonhuman primates, with a high fatality rate ranging from 60% to 90% . The Zaire ebolavirus (EBOV) is one of the most virulent species of the Ebola virus, and it has been the cause of several deadly outbreaks.
The VP40 protein is a matrix protein that plays a crucial role in the assembly and budding of the Ebola virus particles . Structurally, VP40 consists of two functionally interrelated domains: an N-terminal oligomerization domain and a C-terminal membrane-binding domain . The protein’s ability to bind to membranes induces a conformational change necessary for its oligomerization. Membrane-associated VP40 forms hexamers, while it can also bind RNA in a sequence-specific manner, forming octameric ring-like structures .
Recombinant VP40 (rVP40) refers to the VP40 protein that has been produced using recombinant DNA technology. This involves inserting the gene encoding the VP40 protein into a suitable expression system, such as mammalian cells, to produce the protein in large quantities. Recombinant VP40 is used in various research applications, including the development of diagnostic assays and vaccines.
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Diagnostic Assays: Recombinant VP40 is used in the development of rapid diagnostic tests for Ebola virus disease (EVD). These tests utilize antibody-based technology to capture and detect the VP40 protein, providing results in less than twenty minutes . Such tests are essential for early diagnosis and containment of the virus, especially in resource-limited settings where traditional polymerase chain reaction (PCR) assays are not feasible .
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Vaccine Development: Recombinant VP40 is also used in the development of vaccines against the Ebola virus. Virus-like particles (VLPs) containing VP40 and the surface glycoprotein GP have been used to create vaccine candidates . These VLPs mimic the morphology of the live virus and can elicit an immune response without causing disease.
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Research: Recombinant VP40 is used in various research studies to understand the molecular mechanisms of Ebola virus assembly, budding, and pathogenicity. For example, studies have shown that VP40 can be secreted in an unconventional manner, independent of the endoplasmic reticulum/Golgi pathway, and this secretion may play a role in the virus’s pathogenicity .
