Porcine respiratory and reproductive syndrome virus (PRRSV) is a major swine pathogen responsible for immense economic loss annually. PRRSV first emerged in North America in the late 1980's in near synchrony with its emergence in Europe as the etiological agent of a novel potent swine disease. Not long after, the virus spread to or was detected in most swine rearing countries making it a problem of global relevance. To date, the evolutionary origin of PRRSV is not known although retrospective serologic screening in herds has indicated the virus circulated in pigs for at least several years prior to its official recognition or "emergence". Several hypotheses have been put forth attempting to explain the advent of PRRS however each has its shortcomings.
One hypothesis on the origin of PRRSV postulated a cross-species event in which the parental PRRSV-like virus resided in a rodent species before crossing over to swine and evolving into PRRSV. Had the isolation of such an ancestral strain been possible, it might have provided the first opportunity to compare genetic differences between the parental strain and PRRSV prototype isolates. The degree of difference would have provided clues to how much genetic change was sufficient to enable establishment in a new species as well as emerge in a virulent fashion. Unfortunately, no such ancestral PRRSV-like virus has been detected.
The first inkling of genetic variability and its relation to virulence can be gauged from the initial emergence itself. Clinical presentation of PRRS in both North America and Europe was considered severe with many presenting symptoms shared. Shockingly, however, sequences of prototype isolates from the two continents differed from each other at more than a third of all aligned genomic sites. As a result, the first lesson was the manifestation of PRRS did not require the causative agent to conform to narrow genetic diversity boundaries. Since the initial outbreaks, there has been a gradual build up sequence deposition of select PRRSV genes in various databases in an effort to assess diversity in the field and keep track on its change. Studies on the overall known diversity from these public databases indicated all isolates to date are entirely related to either one of the two prototype isolates (hence the designation of two genotypes). No intermediates have been detected. Nonetheless, there is still substantial genetic diversity within each genotype (more so in type 1 than type 2). With respect to each genotype, time to time there are reports of particularly "virulent" outbreaks. However, one the major hurdle in linking change in genetic diversity to degree of virulence is the lack of a standardized scheme of assessing virulence without which making meaningful comparisons across outbreaks temporally and spatially is problematic. The other major hurdle is most sequencing information available pertains to a very limited region of the PRRSV genome which may not necessarily hold the information to genetic changes linked to altered virulence.
Despite the drawbacks above, there are some examples in which a change in genetic diversity resulted in particularly virulent outbreaks of PRRS. All the examples that follow demonstrate scenarios in which there is clear evidence from PRRSV phylogenetics that virulent outbreak isolates were distinct from either known endemic diversity or diversity for which herds were vaccinated. Global type 2 PRRSV phylogeny indicates PRRSV was first introduced into China as a single event from North America around the mid-90's which gradually led to it becoming endemic. In 2006, "High Fever" PRRS broke out which spread across most of the country affecting up to 2 million pigs. All outbreak isolates from the period were closely related to each other but clearly distinct from the endemic diversity from which they had emerged. The second example is of the "abortion storm" that was reported in 1996. This time phylogenetics indicated isolates belonged to independent outbreaks but all of which were of evolutionary lineages significantly different to those on which the vaccines were designed that had been administered to the herds prior. The third example is from the MN184-related outbreak in Minnesota and other regions in 2001. Once again, isolates from the outbreak all clustered together but not with endemic diversity in the region. This was surprising as there was an active surveillance effort in monitoring the genetic diversity of the region which made it difficult to explain the sudden change in diversity. Later on, it was demonstrated that outbreak isolates were closely related to circulating diversity in Ontario, Canada. A sudden introduction from up north explained the lack of immediate relatedness to local diversity while simultaneously showing how a change in genetic diversity to which herds were normally exposed to triggered a virulent episode of PRRS. In summary, there is clear indication of PRRS being variable in its severity and it is now generally believed this variability is at least partly the result of extensive genetic diversity amongst circulating PRRSV strains in the field. In order to progress towards finely delineating the viral genomic sites associated with changes in pathogenicity, steps need to be taken to standardize virulence evaluation as well as switch to more comprehensive PRRSV sequence surveillance and complete viral genome sequencing.