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Development and optimization of biologically contained Marburg virus for high-throughput antiviral screening
Bert Vanmechelen1, Joren Stroobants2, Winston Chiu2
1Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratory of Clinical and Epidemiological Virology, KU Leuven, Herestraat 49 - box 1040, 3000, Leuven, Belgium.
Abstract:
Comparable to the related Ebola virus, Marburg virus is an emerging zoonotic pathogen that causes hemorrhagic fever with a high mortality rate. Therefore, handling of Ebola virus and Marburg virus is limited to biosafety level 4 facilities, of which only a limited number exists worldwide. However, researchers have developed several virus alternatives that are safe to handle in lower biosafety settings. One particularly interesting approach is the engineering of biologically contained Ebola virus by removing an essential gene from the virus genome and providing this missing gene in trans in a specific cell line. Because the virus is confined to this specific cell line, this results in a system that is safe to handle. So far, Ebola virus is the only virus for which biological containment has been reported. Here, we describe the first successful rescue of biologically contained Marburg virus and demonstrate that biological containment is also feasible for other filoviruses. Specifically, we describe the development of containment cell lines for Marburg virus through lentiviral transduction and show the growth and safety characteristics of eGFP-expressing, biologically contained Marburg virus in these cell lines. Additionally, we exploited this newly established Marburg virus system to screen over 500 compounds from available libraries. Lastly, we also validated the applicability of our biologically contained Marburg virus system in a 384-well format, to further illustrate the usefulness of this novel system as an alternative for high-throughput MARV screening of compound libraries.
Insights
Researchers developed biologically contained Marburg virus (MARV), a safer alternative for handling this deadly pathogen. This breakthrough enables high-throughput screening of compounds in lower biosafety settings.
Area of Science:
- Virology
- Pathogen Safety
- Molecular Biology
Background:
- Marburg virus (MARV) is a zoonotic pathogen causing severe hemorrhagic fever with high mortality.
- Handling MARV requires stringent biosafety level 4 (BSL-4) containment, limiting research accessibility.
- Existing MARV research is constrained by the scarcity of BSL-4 facilities worldwide.
Purpose of the Study:
- To establish the first biologically contained Marburg virus system for safe research in lower biosafety levels.
- To demonstrate the feasibility of biological containment for filoviruses beyond Ebola virus.
- To develop a novel platform for high-throughput screening of antiviral compounds against MARV.
Main Methods:
- Engineering a Marburg virus with a deleted essential gene, complemented in trans by a specific cell line.
- Developing Marburg virus containment cell lines using lentiviral transduction.
- Characterizing the growth and safety of enhanced green fluorescent protein (eGFP)-expressing, biologically contained Marburg virus.
- Screening over 500 compounds using the established Marburg virus system in a 384-well format.
Main Results:
- Successful rescue and characterization of biologically contained Marburg virus.
- Demonstrated safety and efficacy of the containment system in lower biosafety settings.
- Validated the system's utility for high-throughput screening of compound libraries.
Conclusions:
- Biological containment is a viable strategy for Marburg virus and potentially other filoviruses.
- The developed Marburg virus system offers a safe and efficient alternative for research and drug discovery.
- This novel system significantly enhances opportunities for high-throughput screening of antiviral compounds against Marburg virus.
