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Updated: May 7, 2026

Production of Pseudotyped Particles to Study Highly Pathogenic Coronaviruses in a Biosafety Level 2 Setting
Published on: March 1, 2019
Pseudovirus mimics cell entry and trafficking of the human polyomavirus JCPyV
Gretchen V Gee1, Bethany A O'Hara, Aaron Derdowski
1Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI 02912, United States.
Abstract:
The normally asymptomatic human polyomavirus, JCPyV, is the causative agent of a rare but fatal demyelinating disease known as progressive multifocal leukoencephalopathy (PML). Individuals at risk for developing PML include those with AIDS, with other underlying immunosuppressive diseases, and in patients treated with immunomodulatory regimens. Drugs to prevent viral reactivation in the setting of immunosuppression or immunomodulation could be used to sustain lives. Development of such drugs has been impeded by the difficulty of growing and studying the virus. We sought to develop a more efficient method for screening drugs that inhibit viral infection. Pseudovirus models have been developed which may be of use in pharmaceutical research. The use of pseudoviruses as models for viral infection is dependent on them using similar pathways for infection as virus. We screened known inhibitors of viral entry for their ability to block pseudovirus infection. Here we show that the pseudovirus based on the human polyomavirus JCPyV recapitulates virus binding, entry and trafficking. This system can be used for high-throughput screening of antiviral drugs.
Insights
A new pseudovirus model for John Cunningham virus (JCPyV) allows for efficient screening of antiviral drugs. This breakthrough aids in developing treatments for progressive multifocal leukoencephalopathy (PML).
Area of Science:
- Virology
- Neuroscience
- Immunology
Background:
- John Cunningham virus (JCPyV) causes progressive multifocal leukoencephalopathy (PML), a fatal demyelinating disease.
- PML risk is elevated in immunocompromised individuals, including those with AIDS or on immunomodulatory drugs.
- Developing antiviral therapies is hindered by challenges in culturing and studying JCPyV.
Purpose of the Study:
- To establish an efficient method for screening drugs that inhibit JCPyV infection.
- To validate a JCPyV pseudovirus system for pharmaceutical research and antiviral drug discovery.
Main Methods:
- Development of a JCPyV-based pseudovirus model.
- Assessment of pseudovirus infection pathways, including binding, entry, and trafficking.
- Screening of known viral entry inhibitors for their efficacy against pseudovirus infection.
Main Results:
- The JCPyV pseudovirus model accurately recapitulates key aspects of viral infection.
- The pseudovirus system demonstrates similar infection pathways to the native virus.
- The model proved effective in identifying inhibitors of viral entry.
Conclusions:
- A JCPyV pseudovirus system provides a viable platform for high-throughput screening of antiviral drugs.
- This system can accelerate the development of novel therapeutics for PML.
- Further research utilizing this model may lead to life-sustaining treatments for JCPyV-related diseases.
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