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Published on: February 8, 2012
Tetraspanin CD9 Is a Positive Regulator of Filovirus Egress
Loveleena K Anand1, Marija A Djurkovic2, Ariel Shepley-McTaggart1
1Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, 3800 Spruce Street, Philadelphia, PA 19104, USA.
Abstract:
Filoviruses, including Ebola (EBOV) and Marburg (MARV) viruses, are zoonotic pathogens that cause severe hemorrhagic fever in humans, with mortality rates reaching up to 90%. Filovirus egress and spread are driven by the viral matrix protein VP40 and regulated both positively and negatively by a growing number of specific host interactors. Here, we identify tetraspanin protein CD9, a plasma membrane organizing and scaffolding protein, as playing a role in facilitating efficient egress of EBOV and MARV. Indeed, we observed a significant decrease in viral egress of VLPs and live filoviruses from CD9-KD cells as compared to that from WT cells. Moreover, exogenous expression of CD9 rescued egress of VP40 VLPs close to WT levels in the CD9-KD cells. These findings identify tetraspanin CD9 as a positive regulator of filovirus egress, and thus CD9 may represent a potential new target for antiviral therapies targeting the late stage of the filovirus lifecycle.
Insights
Tetraspanin CD9 facilitates the efficient egress of Ebola (EBOV) and Marburg (MARV) viruses. This finding identifies CD9 as a potential target for developing new antiviral therapies against filoviruses.
Area of Science:
- Virology
- Cell Biology
- Immunology
Background:
- Filoviruses, such as Ebola (EBOV) and Marburg (MARV) viruses, are zoonotic pathogens causing severe hemorrhagic fever with high mortality rates.
- Viral egress and spread are orchestrated by the matrix protein VP40 and modulated by host-cell interactions.
Purpose of the Study:
- To investigate the role of tetraspanin CD9 in the egress of EBOV and MARV.
- To identify CD9 as a potential therapeutic target for filovirus infections.
Main Methods:
- Utilized CD9-knockdown (KD) cells and wild-type (WT) cells to assess viral egress.
- Quantified the egress of virus-like particles (VLPs) and live filoviruses.
- Assessed the rescue effect of exogenous CD9 expression on viral egress.
Main Results:
- A significant reduction in viral egress was observed in CD9-KD cells compared to WT cells.
- Exogenous expression of CD9 restored VP40 VLP egress in CD9-KD cells to levels near those in WT cells.
- Tetraspanin CD9 acts as a positive regulator of filovirus egress.
Conclusions:
- Tetraspanin CD9 plays a crucial role in facilitating efficient filovirus egress.
- CD9 represents a potential novel target for antiviral strategies aimed at inhibiting the late stages of the filovirus lifecycle.
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