VanderWaal: Expect to see new PRRS sublineages emerge
US pig producers know that many different strains of porcine reproductive and respiratory syndrome (PRRS) exist, and that immunological cross-protection amongst different strains can be variable. However, the continual emergence of new sub-lineages continues to destabilize progress towards PRRS control, said Kim VanderWaal, PhD, associate professor at the University of Minnesota.
In recent work, VanderWaal and her colleagues have analyzed more than 20,000 PRRS sequences from the University of Minnesota Veterinary Diagnostic Laboratory to reveal the evolutionary dynamics of PRRS. In the past decade, there has been an explosion in the evolution of viruses belonging to Lineage 1, which is a viral family that includes restriction fragment length polymorphism (RFLP)-types 1-7-4 and 1-8-4, among others. The diversity of Lineage 1 became large enough (based on US data) that it needed to be sub-divided into eight distinct sub-lineages, she said, but there are likely additional sub-lineages circulating in other parts of the world.
An RFLP is a type of polymorphism that results from variation in the DNA sequence recognized by restriction enzymes. These are bacterial enzymes used by scientists to cut DNA molecules at known locations, according to www.genome.gov.
“Our research shows that there is a new dominant sub-lineage every three years or so,” she told Pig Health Today. “The emergence of the L1C-1-4-4 variant actually follows this cycle quite well, based on when and how different sub-lineages have emerged and spread in the past.”
PRRS is a ribonucleic acid (RNA) virus, and as such, it has a high rate of evolution. “Even among RNA viruses, the rate at which PRRS changes is exceptionally high,” VanderWaal said. “While there are many reasons why the PRRS virus is difficult to control, its rapid rate of change generates a great deal of genetic diversity, which also makes it very antigenically diverse.”
This makes it more challenging to achieve good cross-protection amongst strains, she pointed out.
VanderWaal and her colleagues are delving into the temporal patterns of sub-lineage emergence. Typically, viruses belonging to different sub-lineages are >7% different in ORF5 gene.
“In the historical data, we do see situations where one sub-lineage seems to grow out of another sub-lineage, but eventually becomes distinct enough that we call it its own sublineage,” VanderWaal explained.
Sub-lineages provide a better classification system to group closely related viruses than RFLP-types. However, sub-lineages are quite large and numerous different variants (groups of viruses <2% different from each other) exist within a sub-lineage. The new variant referred to as L1C-1-4-4 is a good example of this, VanderWaal said.
“If you just use 1-4-4, that particular RFLP type exists in a lot of different lineages. Similarly, lineage 1C is quite large, so it’s not specific enough to define this new PRRS variant that we’re talking about. As a result, we’re using both the sub-lineage and RFLP type to refer to this variant,” she said.
“As of now, we are not calling novel L1C-1-4-4 variant a new sub-lineage, but the early evolutionary dynamics and the rate at which it’s expanding from an evolutionary perspective do resemble the early periods of emergence of other sub-lineages over the last decade. It looks like it potentially could become its own sub-lineage, but for now we’ll keep watching.”
Researchers at the University of Minnesota have looked at the whole genome of the new PRRS variant, and according to VanderWaal, it appears to have some evidence of recombination so that’s another factor they hope to delve into further.
Future research needs
“We have ample evidence right now that suggests that emergence of novel sub-lineages or novel variants could be potentially related to immunity in the population, but we haven’t done the full workup in the lab from an immunological standpoint to confirm that,” VanderWaal said. “We’d like to see more studies on PRRS cross-protection between different sublineages.”
In addition, while classification of PRRS viruses into lineages based on the ORF5 gene seems to translate relatively well to the whole genome, far less is understood about whole-genome data. As researchers start interpreting whole-genome data, they will encounter questions on why particular genetic differences matter, VanderWaal explained. In addition, the genetic determinants of virulence or of cross-protection are not fully understood, so further research is needed.
Posted on February 1, 2022