PRRS Research Update

Exploring Canadian research findings & benchmark goals.

by Kristen Lutz

“As a population that’s interested in animal health, we’ve been trying to solve the porcine reproductive and respiratory syndrome virus (PRRS) for decades. We’ve had some successes but it’s complicated,” says Zvonimir Poljak, DVM, associate professor with the Ontario Veterinary College.

PRRS has swept through North America since the late 1980s and scientists continue to investigate it, particularly the genetics of the disease.

Both the maternal-fetal interface and the viral genetics are currently being researched to aid in reduced transmission and a better understanding of the virus.

Maternal-fetal relationship

John Harding, professor in the Department of Large Animal Clinical Sciences at the University of Saskatchewan, has been researching the reproductive form of PRRS for over 10 years. In 2011, Harding’s team started their research and has since published over 30 scientific papers. His research is ongoing.

piglets feeding
    Understanding how the virus passes from dam to fetus will help scientists determine genetic markers - Jodie Aldred photo

Harding says that one of his areas of study, transmission from dam to the fetus, was initially theorized over 30 years ago. “It goes back to the three theories that were proposed by a couple of researchers in early 1990s soon after the PRRS virus was first discovered,” he explains.

“After the virus infects the dam it makes its way to the uterine tissues very quickly – within a day – and then it has to cross through the placental barrier and into the fetus,” he says.

Harding explains that this mode of transmission is highly complicated. The virus would have to pass through the maternal and fetal epithelium (where the placenta attaches to the uterus) before infecting the fetus.

How is the virus able to accomplish this? And if we can understand its mechanisms, can we stop the viral spread between the dam and fetus? Harding says this relates back to some of the first research done on PRRS. “In the early 1990s, soon after the PRRS virus was first discovered, (researchers) proposed three routes of transplacental transmission in their early papers,” he explains, noting the three hypothesized ways in which the fetus becomes infected.

hands separating fetal placenta
    Scientists are investigating cells in the placental endometrium to better understand transplacental transmission - Jodie Aldred photo

“The third way, which is most commonly agreed upon, is the virus enters an immune cell called the macrophage, that macrophage then moves towards the epithelium and squeezes itself between the individual epithelial cells into the placenta where it can access the fetal umbilical cord and enter the fetus.”

Another theory is the virus infects the fetus by directly entering and passing through each of the two epithelial cell layers.

“We’ve been able to locate and use a trophoblastic cell line (cells collected from the surface of a 12-day-old embryo) and have shown in the labratory that the PRRS virus can enter the epithelial cell. It can’t replicate, but it can also exit the epithelial cell and still infect cells that are susceptible,” says Harding. “This is significant because the PRRS virus requires a receptor at the cell’s surface to enter the cells. There are a couple of receptors used but the most important one is CD163. However, CD163 is not present on the epithelial cells.”

Harding continues to explain that the CD163 receptor on the macrophage surface enables the virus to enter the cell and is required for viral replication or reproduction.

These macrophage cells are the virus factories and regardless of the mechanism used by the virus to infect the fetus, there is a lot of virus present near the junction of the uterus and placenta in as little as 24 to 48 hours. He feels that the mechanism of infection probably involves an established path related to nutrient transfer to the growing fetus.

Genetic resilience

Harding and his research team is also studying “fetal responses, specifically what is killing the fetus, and genetic markers of fetal resilience. We’ve discovered several and have ongoing research with the marker we feel is most promising.”

Regarding current research pertaining to genetic markers, Harding feels it can be hypothesized that one or more single nucleotide polymorphism (SNP) could aid in building genetic resilience against PRRS. “In our first study of 1,000 fetuses, we were able to conduct a genome-wide association study of fetal survival, fetal viability and fetal viral load. We found a number of SNPs related to more favourable fetal outcomes. The SNP that we chased, because it was the lowest hanging fruit, was related to fetal viability.

“The animals that were homozygous with the rare allele had the increase in fetal viability. The position of that SNP pointed to a couple genes involved in thyroid hormone regulation,” he continues.

Harding explains that the viability SNP led them to discover that the PRRS virus causes a transient hypothyroidism. They initially thought if they could supplement thyroid hormones, perhaps this would decrease the effects of the PRRS virus infection, but this was not the case.

Harding and his team are continuing to investigate the significance of this SNP and the potential it may have in controlling the PRRS virus and the disease.

The ultimate goal is to breed for resilience. Harding is hoping that by finding the mechanisms in which the virus crosses the maternal-fetal interface, and understanding which genes may be related to resilience, there could be potential to breed for certain traits and control the transmission of the virus.

“Before we started there were very few scientific papers on reproductive PRRS, and now we have a much better understanding of the effects of the virus in the pregnant dam and fetus. But PRRS researchers are never going to be short of research questions anytime soon,” he concludes.

Virus genetics

In opposition to maternal and fetal genetics, Poljak researches the genetics of the virus itself. “We’re sequencing a tiny portion of the PRRS virus and saying that it belongs to a certain strain. But we can access this detailed, small portion of the genome and determine how bad the PRRS virus will be in that specific strain,” he says.

Poljak’s lab is still heavily researching this and has a current understanding which improves the accuracy of estimation of severity by 15 per cent.

“Are we happy with the performance? Not quite. And there are multiple reasons why we’re not happy with this. Of course, we would like to be as accurate as possible and I think there are multiple reasons why we can’t be more accurate at this time. One of the reasons is that in addition to genetic information, we’re also collecting information about management factors and demographic factors,” Poljak explains.

He says that not all of this information is collected with high precision, which can lead to a lower overall accuracy rate. He also explains that the artificial intelligence technology being used requires a large data set in order to be more exact with its severity determinations.

pig standing in drift of pigs
    Martin Schwalbe photo

He is hoping, with more data collection over the years, to develop a program for producers and veterinarians – “something of a prognostic. So, you can imagine some sort of a system that would help someone in the production system, with a high degree of certainty and accuracy, how bad PRRS is going to be in the production system. If we do this with high accuracy, then people are going to adjust their management strategies and that can ultimately be used for the benefit of producers.

“So, you can imagine a system where the genetic information is provided to determine how much clinical impact there is going to be.

“Then the producer provides certain demographic factors, such as the size of the population of sows and maybe genetics or breed of the animals, the season that you’re in and what is the immunity against the PRRS virus in that herd. And with all this information you can predict how severe and how clinically impactful this outbreak is going to be.”

This would then be used as a tool for veterinarians and producers to help guide them in their management decisions.

With significant research such as the studies listed above, a better understanding of the virus can help aid producers in viral management with the potential to breed for resilience in the future. BP

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