December 8, 2015
Researchers from the University of Missouri, Kansas State University and Genus plc have not just embarked on a game changer for combating porcine reproductive and respiratory syndrome virus, but perhaps have discovered the actual genetic showstopper – PRRS-resistant pigs.
Since it was first detected in the United States in 1987, PRRS has cost the global hog industry dearly – an estimated $6 million per day worldwide. Raymond “Bob” Rowland, professor of diagnostic medicine and pathobiology in the College of Veterinary Medicine at Kansas State University and collaborator on the project says, “We have seen the disease two ways which has always been puzzling about the disease. We have seen it as infection storm in which it is just a train wreck that just wipes out a sow farm. We also have seen it as deaths by 1,000 cuts. Pigs do not perform as well. You have to keep them on feed a couple weeks longer to get them up to market weight. It is a disease that has been well-adapted to modern production.”
PRRS has always been a disease that can evolve with the changing management practices, which is the frustrating part. Rowland knew in the 1990s, based on his experience, it is a disease that would keep coming back over and over again. Over the years, the industry approach and perspective have changed from state of denial to tolerating the disease to finding a solution.
Many facets of PRRS research and technology are in the works from industry partners, universities and private companies to unlock the mystery of how the virus infects the pigs and how to stop it dead in its track. Through revolutionary gene-editing technology, a team of researchers led by Randall Prather, animal science professor from the University of Missouri, was able to isolate the protein, CD163, which helps PRRS to spread throughout the pig.
Previously, researchers believed that the virus entered pigs by being inhaled into the lungs, where it attached to a protein known as sialoadhesin on the surface of white blood cells in the lungs. However, two years ago Prather’s and Rowland’s groups worked together to show that elimination of sialoadhesin had no effect on susceptibility to PRRS. A second protein, called CD163, was thought to “uncoat” the virus and allow it to infect the pigs. In their current study, Prather’s team, using the progressive CRISPR/Cas9 system to perform gene-editing, worked to stop the pigs from producing CD163. As Prather simply explains, “If the CD163 protein is not there to “uncoat” the virus, the pigs do not see it and the pigs do not get sick.”
While the pigs that didn’t produce CD163 didn’t get sick, scientists also observed no other changes in their development compared to pigs that produce the protein. “It is absolutely amazing these pigs are running around in a pen together coughing on each other and the pigs with the genetic edits still do not get sick,” Prather adds.
Whereas the important genetic research was completed in Prather’s lab, the research needed to be tested by completing challenge experiments. A task passionately took on by a team of K-State researchers spearheaded by Rowland. Over the years, Rowland’s team has exposed thousands of pigs to PRRS trying to find pigs naturally resistant to PRRS and until now he has not found that particular animal.
In this particular project, the K-State team took the pigs and infected them with PRRS. These pigs were co-mingled with susceptible, non-gene edited pigs. There was no way physically beyond an identification tag to tell the pigs apart. The researchers completed the virus replication analysis and looked for any immune response.
Sitting on a beach in Florida, Rowland received the good news from technicians at his lab. It turned out that the three pigs that had the CD163 molecule knocked out of their genetic code at Prather’s lab exhibited no signs or scientific evidence of being infected with PRRS.
The early stage results of this research are extremely promising not only from an economically standpoint but also for the well-being of the actual pig.
“There are millions of animals that die prematurely, needlessly. Just think of all the extra input that when into creating these animals and now it is a waste. So, when we talk about sustainability and animal well-being this is a really important discovery,” Prather says.
Realizing the importance to address the disease, British-based biotechnology company Genus plc has invested deeply in the research.
Starting his career as a graduate student researching the PRRS virus, Bill Christianson, Genus chief operating officer, understands the toll the virus has taken on hog farmers around the globe.
For the most part, it is a global phenomenon. The vast majority of pig-producing countries around the world deal with PRRS one way or another,” Christianson says. “The frustration has been control strategies that might work on individual herds or individual units for some particular producers don’t work for all. This gives us the chance to use technology that will make a significant difference.”
He adds, “I have been around long enough to know that a lot of these things (PRRS strategies) are sort of partial shades of gray where these initial results are pretty black and white. These pigs are completely resistant.”
He and Jonathan Lightner, chief scientific officer and head of R&D, stress the importance of his company to fund different disease research tactics. “Genus has been really working on research approaches to potentially solving the challenges presented by PRRS for over 10 years now,” Lightner explains.
The company has been collaborating with Prather and other researchers to identify potential targets to produce resistance to PRRS. This particular investment in precise gene-editing research will be beneficial for the entire hog industry.
The University of Missouri has signed an exclusive global licensing deal for potential future commercialization of virus-resistant pigs with Genus plc. Together, the research will eventually be put to the test on commercial hog farms.
If the development stage is successful, Genus will seek any necessary approvals and registration from governments before a wider market release.
Still, Lightner stresses it will take time before PRRS-resistant pigs will be in barns of commercial hog operations. “We are several years to market – likely five or more. Our aspiration for this technology once it is advances through the development phase and any necessary regulatory approvals is that it will be available as part of a genetic package that we will provide through our PIC business.”
Christianson further explains that Genus as a company focuses on doing the right thing that is responsible and it is important to be transparent moving forward with the research. In due time, the company will complete the necessary regulatory process being upfront and open.
It is important to note that Prather’s work is editing DNA that already naturally occurs in the pig. The process is simulating nature quickly to solve a crucial problem. As Rowland further explains, “If we wait 10,000 years this might be something that naturally occurs. This is how animals become resistant to things. They are exposed and then through mutation and selection they become resistant. What we have done is accelerated the process. We have taken a rational approach.”
Essentially, this technology is making the pig healthy. In terms of an animal welfare issue, if PRRS can be “taken off the table” an important advancement in pig health has been made, further explains Rowland.
“This technology is not only applicable to PRRS but could be applied to other infectious diseases as well,” Rowland says. “At the end of the day, we are making the pig healthier and in some respect create other opportunities to protect the public.”
The study has been published in Nature Biotechnology this past Monday.
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