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Downregulation of beta1 integrins by Ebola virus glycoprotein: implication for virus entry
1Laboratory of Microbiology, Graduate School of Veterinary Medicine, Sapporo, 060-0818, Japan.
Abstract:
Filoviruses, including Ebola virus, are cytotoxic. To investigate the role of the Ebola virus glycoprotein (GP) in this cytopathic effect, we transiently expressed the GP in human kidney 293T cells. Expression of wild-type GP, but not the secretory form of the molecule lacking a membrane anchor, induced rounding and detachment of the cells, as did a chimeric GP containing its ectodomain and influenza virus hemagglutinin transmembrane-cytoplasmic domain. These results indicate that the GP ectodomain and its anchorage to the membrane are required for GP-induced morphologic changes in host cells. Since cell rounding and detachment could be associated with reduced levels of cell adhesion molecules, we also studied the expression of integrins, which are major molecules for adhesion to extracellular matrices, and found that the beta1 integrin group is downregulated by the GP. This result was further extended by experiments in which anti-beta1 monoclonal antibodies or purified integrins inhibited the infectivity of vesicular stomatitis virus pseudotyped with the GP. We suggest that integrins, especially the beta1 group, might interact with the GP and perhaps be involved in Ebola virus entry into cells.
Insights
Ebola virus glycoprotein (GP) causes cell damage by altering cell shape and adhesion. This viral protein downregulates beta1 integrins, potentially aiding virus entry into host cells.
Area of Science:
- Virology
- Cell Biology
- Molecular Biology
Background:
- Filoviruses, such as Ebola virus, exhibit cytotoxic effects on host cells.
- The Ebola virus glycoprotein (GP) is a key viral component mediating host cell interactions.
Purpose of the Study:
- To investigate the role of Ebola virus glycoprotein (GP) in cellular damage and identify its molecular mechanisms.
- To determine if GP expression induces specific morphologic changes in host cells.
Main Methods:
- Transient expression of wild-type and chimeric Ebola virus GP in human kidney 293T cells.
- Analysis of cell morphology (rounding, detachment) and expression of cell adhesion molecules, specifically beta1 integrins.
- Functional assays using anti-beta1 monoclonal antibodies and purified integrins to assess viral infectivity.
Main Results:
- Expression of wild-type GP, but not its secretory form, induced cell rounding and detachment.
- GP anchorage to the cell membrane and its ectodomain were essential for inducing these morphologic changes.
- GP expression led to the downregulation of beta1 integrins.
- Inhibition of beta1 integrins or their interaction with GP reduced the infectivity of pseudotyped viruses.
Conclusions:
- Ebola virus GP induces cytopathic effects through mechanisms involving cell adhesion molecule downregulation.
- Beta1 integrins are implicated in the interaction with Ebola virus GP and may play a role in viral entry into host cells.