By Diane DeWitte, UMN Extension swine educator
Originally printed in The LAND - as May 12, 2025 Swine & U column
Producers who were raising pigs in the 1980s can clearly remember the first time they encountered the “Mystery Swine Disease,” a deadly virus that affected both breeding and finishing hogs and changed the landscape of pig production forever. First found in herds in Indiana, North Carolina, Minnesota and Iowa, it was soon named Porcine Reproductive & Respiratory Syndrome (PRRS). Historically, conservative estimates are that PRRS virus costs the U.S. swine industry more than $687 million per year (Holtkamp et al, 2013).
Kim VanderWaal, associate professor in the Department of Veterinary Population Medicine at CVM, led the project which studied the evolution of the PRRS virus and identified drivers of genetic diversity in viruses in humans and other animals.
The project utilized one-of-a-kind data already collected by the Morrison Swine Health Monitoring Project at the University of Minnesota, which tracks the occurrence of PRRSV in roughly 50% of the United States’ breeding swine population. MSHMP is coordinated by Cesar Corzo, Leman Chair of Swine Health & Productivity and associate professor in the VPM department, who is also deeply involved in PRRSv research with the team.
Another specific asset to the team’s approach included the contributions of Declan Schroeder, virologist and associate professor in the department of VPM. Schroeder’s lab developed a technique that described the full genomic strain profile of PRRSV within 24 hours of sampling. Schroeder’s technique gave veterinarians a better tool to rapidly diagnose the PRRS infection in animals.
With the emergence of new PRRS strains every three to five years, this project began to track the spread and development of newly evolved strains as well.
The genome is an organism’s complete set of DNA. “If the DNA is a set of instructions carefully organized into paragraphs (genes) and chapters (chromosomes), then the entire manual start-to-finish is the genome.” (genome.gov, 2025)
In biology, phylogeny is the evolutionary history of a group of related organisms and is represented by the phylogenetic tree that shows how species are related to each other.
The clade is a grouping that includes a common ancestor and all the descendants of that ancestor. The word clade (kládos) “branch” from the Greek is known as a monophyletic or natural group. (https: evolution.berkeley.edu)
A variant is an alteration in the most common DNA sequence and is increasingly used in place of the term “mutation”. (www.cancer.gov)
PRRS is one of the most rapidly evolving viruses in the world. Even compared to other RNA viruses, the rate of change is exceptionally high for PRRSV, with close to 1% of the genome experiencing point mutations per year. Not all mutations have an equal impact, but one can expect a general trend where viral attributes, for example, immunology or virulency, shift gradually through time as mutations.
Another evolutionary mechanism of viruses is recombination. In hosts that are co-infected with two variants, portions of the viral genomes from each variant may be interchanged or “re-combined” during replication, resulting in offspring that are a genetic mosaic of the two parental variants. In contrast to point mutations, recombination results in a sudden shift in the genome composition of a virus.
Researchers believe that recombination is likely a common phenomenon that occurs in herds co-infected by multiple PRRSV variants, but recombination may go undetected in the absence of intensive whole genome sampling. While recombination plays a role in PRRSV evolution and that some emerging variants are recombinants, current understanding of the genetic determinants of viral characteristics, such as virulence or cross-immunity, does not allow researchers to predict the impact of recombination.
Scientists have two basic tools for understanding PRRSV evolution: sequencing of the ORF5 gene, and whole genome sequencing. Both tools can help answer questions about the evolution and the epidemiology of a particular PRRSV variant, and the choice of tool will depend on the question. ORF5 gene sequencing is much more straightforward to analyze and interpret and whole genome sequencing (WGS) data is complex and needs an expert to interpret.
The most common reasons that veterinarians submit samples for sequencing are to a) distinguish between a resident and new variant on the farm and attempt to determine the possible source of introduction, and b) track the spread of novel PRRS variants. For these questions, ORF5 often will provide a sufficient answer and WGS may not add a great deal of additional insight. The choice of tool depends on the question and aims of the practitioner.
The rapid evolution and diversity of PRRSV are two key complicating factors to controlling the disease. The additional circulation of numerous genetic variants creates recurring epidemic-like waves that spread quickly and widely through the swine industry, making it the most important endemic swine disease farmers encounter. Next month we will learn more about the success of UMN’s genomic sequencing research.
Pamornchainavakul, Nakarin, Mariana Kikuti, Igor A. D. Paploski, Dennis N. Makau, Pamornchainavakul, N., Kikuti, M., Paploski, I. A. D., Makau, D. N., Rovira, A., Corzo, C. A., & VanderWaal, K. (2022). Measuring How Recombination Re-shapes the Evolutionary History of PRRSV-2: A Genome-Based Phylodynamic Analysis of the Emergence of a Novel PRRSV-2 Variant. Frontiers in Veterinary Science, 9. doi:10.3389/fvets.2022.846904
Paploski, I. A., Pamornchainavakul, N., Makau, D. N., Rovira, A., Corzo, C. A., Schroeder, D. C., . . . VanderWaal, K. (2021). Phylogenetic Structure and Sequential Dominance of Sub-Lineages of PRRSV Type-2 Lineage 1 in the United States. Vaccines, 9(6), 608.
Some information presented in this article was summarized from a keynote presentation at the 2023 Allen D. Leman Swine Conference, “Chasing a moving target: Rapid evolution and spread of PRRSV in the U.S.”
Diane DeWitte is a UMN Extension Educator based in Mankato, MN. She can be reached at stouf002@umn.edu.
Producers who were raising pigs in the 1980s can clearly remember the first time they encountered the “Mystery Swine Disease,” a deadly virus that affected both breeding and finishing hogs and changed the landscape of pig production forever. First found in herds in Indiana, North Carolina, Minnesota and Iowa, it was soon named Porcine Reproductive & Respiratory Syndrome (PRRS). Historically, conservative estimates are that PRRS virus costs the U.S. swine industry more than $687 million per year (Holtkamp et al, 2013).
SIX YEARS AGO SEEMS A LIFETIME!
In 2019 University of Minnesota College of Veterinary Medicine (CVM) researchers, and collaborators at the University of Edinburgh’s Roslin Institute, received a nearly $3 million grant to investigate how porcine reproductive and respiratory syndrome (PRRS) virus evolves and spreads. The project was designed to help scientists and producers anticipate a herd’s susceptibility to different strains of PRRSv and customize mitigation efforts accordingly. Use of specific strain information assisted researchers in developing specific vaccines. The 4-year grant was jointly funded by the National Institute of Food and Agriculture, National Science Foundation, National Institutes of Health, and the United Kingdom Government’s Biotechnology and Biological Sciences Research Council.Kim VanderWaal, associate professor in the Department of Veterinary Population Medicine at CVM, led the project which studied the evolution of the PRRS virus and identified drivers of genetic diversity in viruses in humans and other animals.
The project utilized one-of-a-kind data already collected by the Morrison Swine Health Monitoring Project at the University of Minnesota, which tracks the occurrence of PRRSV in roughly 50% of the United States’ breeding swine population. MSHMP is coordinated by Cesar Corzo, Leman Chair of Swine Health & Productivity and associate professor in the VPM department, who is also deeply involved in PRRSv research with the team.
Another specific asset to the team’s approach included the contributions of Declan Schroeder, virologist and associate professor in the department of VPM. Schroeder’s lab developed a technique that described the full genomic strain profile of PRRSV within 24 hours of sampling. Schroeder’s technique gave veterinarians a better tool to rapidly diagnose the PRRS infection in animals.
With the emergence of new PRRS strains every three to five years, this project began to track the spread and development of newly evolved strains as well.
TERMINOLOGY IS EVERYTHING
My own recent work learning more about the H5N1 virus has led me into a sector of unfamiliar language. When discussing viruses, the terms genome, tree, clade, variant repeatedly appear.The genome is an organism’s complete set of DNA. “If the DNA is a set of instructions carefully organized into paragraphs (genes) and chapters (chromosomes), then the entire manual start-to-finish is the genome.” (genome.gov, 2025)
In biology, phylogeny is the evolutionary history of a group of related organisms and is represented by the phylogenetic tree that shows how species are related to each other.
The clade is a grouping that includes a common ancestor and all the descendants of that ancestor. The word clade (kládos) “branch” from the Greek is known as a monophyletic or natural group. (https: evolution.berkeley.edu)
A variant is an alteration in the most common DNA sequence and is increasingly used in place of the term “mutation”. (www.cancer.gov)
PRRS is one of the most rapidly evolving viruses in the world. Even compared to other RNA viruses, the rate of change is exceptionally high for PRRSV, with close to 1% of the genome experiencing point mutations per year. Not all mutations have an equal impact, but one can expect a general trend where viral attributes, for example, immunology or virulency, shift gradually through time as mutations.
Another evolutionary mechanism of viruses is recombination. In hosts that are co-infected with two variants, portions of the viral genomes from each variant may be interchanged or “re-combined” during replication, resulting in offspring that are a genetic mosaic of the two parental variants. In contrast to point mutations, recombination results in a sudden shift in the genome composition of a virus.
Researchers believe that recombination is likely a common phenomenon that occurs in herds co-infected by multiple PRRSV variants, but recombination may go undetected in the absence of intensive whole genome sampling. While recombination plays a role in PRRSV evolution and that some emerging variants are recombinants, current understanding of the genetic determinants of viral characteristics, such as virulence or cross-immunity, does not allow researchers to predict the impact of recombination.
Scientists have two basic tools for understanding PRRSV evolution: sequencing of the ORF5 gene, and whole genome sequencing. Both tools can help answer questions about the evolution and the epidemiology of a particular PRRSV variant, and the choice of tool will depend on the question. ORF5 gene sequencing is much more straightforward to analyze and interpret and whole genome sequencing (WGS) data is complex and needs an expert to interpret.
The most common reasons that veterinarians submit samples for sequencing are to a) distinguish between a resident and new variant on the farm and attempt to determine the possible source of introduction, and b) track the spread of novel PRRS variants. For these questions, ORF5 often will provide a sufficient answer and WGS may not add a great deal of additional insight. The choice of tool depends on the question and aims of the practitioner.
WHAT’S HAPPENING NOW?
In 2024 Dr. VanderWaal’s team was awarded a four-year, $800,000 Agriculture and Food Research Initiative grant from the USDA and the National Institute of Food and Agriculture. The study will create an “integrative data science” platform to predict the ability of PRRSV-2 variants to provoke an immune response and spread across farms. The platform will use interconnected machine learning tools from structural biology, computational immunology and genomic epidemiology.The rapid evolution and diversity of PRRSV are two key complicating factors to controlling the disease. The additional circulation of numerous genetic variants creates recurring epidemic-like waves that spread quickly and widely through the swine industry, making it the most important endemic swine disease farmers encounter. Next month we will learn more about the success of UMN’s genomic sequencing research.
REFERENCES
Pamornchainavakul, N., Paploski, I. A. D., Makau, D. N., Kikuti, M., Rovira, A., Lycett, S., . . . VanderWaal, K. (2023). Mapping the Dynamics of Contemporary PRRSV-2 Evolution and Its Emergence and Spreading Hotspots in the U.S. Using Phylogeography. Pathogens, 12(5). doi:10.3390/pathogens12050740.Pamornchainavakul, Nakarin, Mariana Kikuti, Igor A. D. Paploski, Dennis N. Makau, Pamornchainavakul, N., Kikuti, M., Paploski, I. A. D., Makau, D. N., Rovira, A., Corzo, C. A., & VanderWaal, K. (2022). Measuring How Recombination Re-shapes the Evolutionary History of PRRSV-2: A Genome-Based Phylodynamic Analysis of the Emergence of a Novel PRRSV-2 Variant. Frontiers in Veterinary Science, 9. doi:10.3389/fvets.2022.846904
Paploski, I. A., Pamornchainavakul, N., Makau, D. N., Rovira, A., Corzo, C. A., Schroeder, D. C., . . . VanderWaal, K. (2021). Phylogenetic Structure and Sequential Dominance of Sub-Lineages of PRRSV Type-2 Lineage 1 in the United States. Vaccines, 9(6), 608.
Some information presented in this article was summarized from a keynote presentation at the 2023 Allen D. Leman Swine Conference, “Chasing a moving target: Rapid evolution and spread of PRRSV in the U.S.”
Diane DeWitte is a UMN Extension Educator based in Mankato, MN. She can be reached at stouf002@umn.edu.
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