SARS-CoV-2 infection and viral fusogens cause neuronal and glial fusion that compromises neuronal activity
1. Introduction to the Study:
- Objective: The goal is to study the effect of viral fusogens on the fusion of neurons using the virus SARS-CoV-2 as a model.
2. Experimentation with 3D Brain Organoids:
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3D Brain Organoids:
- These are miniature, simplified versions of the brain grown in a lab from stem cells, which are cells capable of becoming many different types of cells.
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Procedure:
- Human Embryonic Stem Cell (hESC): These are stem cells derived from human embryos, which have the potential to turn into any cell type in the body.
- Neuronal Syncytia: This term refers to clusters of cell bodies that result from the fusion of individual neurons.
3. Exploration of Viral Fusogens:
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Viral Fusogens:
- These are proteins from viruses that help in merging the membrane of the virus with the membrane of the host cell, allowing the virus to enter the host cell.
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Key Fusogens Studied:
- Spike S Protein: A protein on the surface of the SARS-CoV-2 virus that binds to a receptor on human cells to initiate fusion.
- p15 Fusogen: A protein from the Baboon Orthoreovirus that can cause cell fusion without needing a specific receptor on the host cell.
4. In Vivo and In Vitro Experiments:
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In Vivo (in living organisms):
- Caenorhabditis elegans: A type of small worm used as a model organism in biological research.
- Transgenic: Refers to organisms that have had genes from another organism inserted into their DNA.
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In Vitro (in artificial environment):
- Human-Derived Neurons: Neurons created in a lab from human cells, used to study human brain function.
5. Implications and Observations:
- Cytoplasmic Material Diffusion:
- The sharing of the internal fluid of cells, which contains all the molecules and structures needed for cell function, between fused cells.
Technical Terms Explained:
- Fusogen: A protein that facilitates membrane fusion.
- Neuronal Fusion: The merging of neurons, leading to sharing of cytoplasmic content.
- hACE2 Receptor: A protein on the surface of many cell types that SARS-CoV-2 uses to enter cells.
- Syncytium: A large cell-like structure formed by the fusion of individual cells.
- Transgenic: Genetically modified organisms with DNA from another organism.
- Pathogenesis: The process by which disease develops in the body.