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Inhibiting Infectious Bronchitis Virus PLpro Using Ubiquitin Variants.
Vera J E van Vliet1,2, Olivia Roscow3, Kihun Kim4
1Molecular Virology Laboratory, Leiden University Center for Infectious Diseases (LUCID), Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.
International Journal of Molecular Sciences
|June 13, 2025
Summary
Novel ubiquitin variants (UbVs) show promise in combating infectious bronchitis virus (IBV) by inhibiting viral protease activity and enhancing innate immunity in chickens, offering a new antiviral strategy.
Area of Science:
- Virology
- Immunology
- Biotechnology
Background:
- Infectious bronchitis virus (IBV) causes significant economic losses in the poultry industry due to its impact on egg production and increased susceptibility to secondary infections.
- Current vaccines offer limited cross-protection against emerging IBV variants, highlighting the need for alternative control strategies like antiviral therapies.
Purpose of the Study:
- To develop novel antiviral strategies against IBV by targeting its papain-like protease (PLpro).
- To investigate the potential of ubiquitin variants (UbVs) as inhibitors of IBV PLpro's deubiquitinating activity and their impact on viral evasion of host immunity.
Main Methods:
- Selection of high-affinity ubiquitin variants (UbVs) targeting IBV PLpro using phage display.
- Assessment of UbVs' inhibitory effect on PLpro deubiquitinating activity.
- Evaluation of viral inhibition in UbV-expressing cells using immunofluorescence microscopy.
Main Results:
- Selected UbVs demonstrated high affinity for IBV PLpro.
- UbVs successfully inhibited the deubiquitinating activity of PLpro, thereby hindering viral immune evasion.
- Immunofluorescence microscopy revealed a significant reduction in IBV infection in UbV-expressing cells (approx. 5%) compared to control cells (approx. 30-40%).
Conclusions:
- Ubiquitin variants represent a potent and innovative antiviral strategy against IBV.
- Targeting IBV PLpro with UbVs shows potential for controlling IBV infections and mitigating economic losses in the poultry sector.
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