A long-term, international collaboration between researchers at the University of Manitoba and the Leiden University Medical Centre in the Netherlands has uncovered vital information about the porcine reproductive and respiratory syndrome virus (PRRSV). This pathogen causes severe disease in pigs, leading to significant economic losses for pork producers across the globe.
“This disease in pigs is important worldwide and is economically fairly significant,” says Marjolein Kikkert, Associate Professor of Virology at Leiden University Medical Centre. “The aim of the project was to improve vaccines for this disease, and it turned out that it was very difficult.” It’s estimated that PRRS costs the Canadian pork industry $130M annually.
Kikkert and collaborator Brian Mark, Dean of the Faculty of Science at the University of Manitoba, looked at targeting a type of protein called a protease. PRRSV uses these proteins to suppress a host’s immune system, causing severe illness. By changing the structure, researchers can design altered viruses upon which to base new vaccines.
With the help of the Canadian Light Source (CLS) at the University of Saskatchewan (USask), Mark and Kikkert were able to visualize the unique structure of the PRRSV protease. What they learned in their study is valuable for developing new vaccines against PRRSV and also helps inform development of vaccines against emerging human viruses.
The team has conducted similar research on coronaviruses — which also use proteases to suppress human and animal immune systems — and has successfully designed new vaccines.
“The trick and hypothesis we had for improving the PRRSV vaccine didn't quite work.” Says Kikkert. “However, we did learn a lot about how these viruses work. And it may certainly be a basis for further work into possibilities for improving vaccines against these viruses and coronaviruses.”
The team’s findings also unlock new doors to understanding how viruses like PRRSV use proteins to replicate, making this a significant academic discovery.
“The Canadian Light Source provided the technology we needed to determine the structures of these proteases, and this knowledge has provided tremendous insight into the biochemistry of these viruses, which is the cornerstone of modern vaccine development,” says Mark.
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Bailey-Elkin, Ben A., Robert CM Knaap, Anuradha De Silva, Ilse M. Boekhoud, Sandra Mous, Niek van Vught, Mazdak Khajehpour, Erwin van den Born, Marjolein Kikkert, and Brian L. Mark. "Demonstrating the importance of porcine reproductive and respiratory syndrome virus papain-like protease 2 deubiquitinating activity in viral replication by structure-guided mutagenesis." PLoS Pathogens 19, no. 12 (2023): e1011872. https://doi.org/10.1371/journal.ppat.1011872
Photos: Canadian Light Source | CMCF Beamline | Researchers
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