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Researcher hopes his work will lead to a more effective vaccine against virus that costs U.S. producers an estimated $600 million a year
BY ANDREW VOWLES
U of G research may point the way toward an improved vaccine against the most important infectious disease facing pork producers in North America.
Prof. Dongwan Yoo, Pathobiology, has learned how a virus infects piglets and pregnant sows to cause porcine reproductive and respiratory syndrome (PRRS). Besides suggesting a way to counter the devastating disease in pigs, his work may also yield clues about how to prevent other viruses from infecting animals and people.
His work is reported in the March cover article of Virology, an edition that also marks the journal's 50th anniversary.
In the United States, PRRS costs pig producers an estimated $600 million US in losses each year; Yoo says that may translate into $60 million worth of losses here in Canada. The National Pork Board in the United States says PRRS — called “swine mystery disease” when it first emerged about 15 years ago — poses the most important disease problem in pigs.
The virus causes abortions in pregnant sows. In piglets, it causes respiratory problems and poor growth. The infection spreads rapidly to affect all sows and piglets on a farm.
Sows with severe cases must be killed. Piglets with mild cases may recover without treatment but have to be kept longer, which means added costs for producers. Although the disease does not affect males, they may shed the virus in their semen — no small matter in an industry heavily reliant on the use of stored semen for artificial insemination, says Yoo.
A vaccine is currently available, but producers and veterinarians question its safety and efficacy. The Guelph researcher hopes his work will lead to a more effective vaccine.
The PRRS virus exists in the host cell cytoplasm, not inside the cell nucleus. But Yoo found that a protein made by the virus crosses into the nucleus to cause the infection.
After isolating the pertinent gene, he used genetic engineering to induce the virus to make a mutant version of the protein. The mutant version differs by only two amino acids but is unable to cross into the cell nucleus.
Yoo studied three groups of pigs: one uninfected, the second given the mutant virus, the third given the unmutated or “wild-type” version.
He and his collaborators, including research associate Douglas Hodgins and PhD student Changhee Lee, then looked for clinical signs in all three groups.
The mutant infected pigs developed less severe disease symptoms and produced higher amounts of neutralizing antibodies. Blood samples taken from this group contained less virus and for a shorter time than did samples taken from pigs given the untreated virus.
“We don't know the exact mechanism of this protein in the nucleus, but by changing these amino acids to prevent the transport of this particular mutant, we produce less severe infection in pigs,” says Yoo.
He now hopes to learn more about how the protein gets into the cell nucleus. He's also studying how the cell produces interferon as a way to combat the infection.
Yoo has filed a patent on his work and says one large American veterinary drug firm is interested in his results.
He's the only Canadian researcher among an international group of scientists funded by the U.S. Department of Agriculture under a four-year, $4.4-million program designed to reduce PRRS in swine herds. Along with other researchers, he has received almost $400,000 US in funding through the program, administered by the University of Minnesota's College of Veterinary Medicine.
Yoo has also received funding from the Natural Sciences and Engineering Research Council of Canada and Ontario Pork.
In his Laboratory for Nidovirus Research at the Ontario Veterinary College, he studies RNA viruses, including the PRRS virus and the related coronavirus responsible for SARS.
“We are leading the research in PRRS at the molecular level,” he says.