By Kim VanderWaal, Ph.D., University of Minnesota

For those outside the pig world, it comes as a surprise that a disease affecting pigs, porcine reproductive and respiratory syndrome virus-2, is one of the most sequenced viruses in the world. But those inside the pig world are unsurprised, because they know that the way sequence data is utilized in swine health management is unparalleled by human medicine. If you, as a human, get infected with the common cold, you are unlikely to even get a diagnosis, let alone will the doctor request a genetic sequence for your particular virus to make decisions about care or treatment.  However, that is exactly what happens when farms break PRRSV-2: the genetic sequence of the virus is often used by animal health professionals for disease monitoring and management.

Figure 1. Number of publicly available sequences (in thousands) of the 30 most sequenced viruses worldwide.  Viruses are colored according to whether they are primarily of concern to veterinary medicine, human medicine, or are a concern due to their zoonotic potential (i.e., transmission from animals to humans).

We recently tabulated all viral sequences that are publicly available in NCBI Genbank. Each viral species was categorized by whether it is a concern primarily for human medicine, veterinary medicine or because it is an animal virus that is of interest due to its zoonotic potential to infect humans. As one might expect, viruses associated with human pandemics, such as SARS-CoV-2, HIV and influenzas are the most sequenced viruses worldwide. However, with more than publicly available 37,000 sequences in 2024, PRRSV-2 sits at 11^th and is by far the highest ranked veterinary virus. 

Furthermore, in the U.S., the vast majority of PRRSV-2 sequences are not in public databases because they have been generated by fee-for-service diagnostic labs as opposed to research or government-sponsored surveillance. Based on the case load of diagnostic labs reported by various papers on PRRSV-2 genetic diversity, the true number of sequences is conservatively >100k - the vast majority of these are sequences of the marker gene, ORF5, as opposed to whole genomes.

In a survey administered by AASV, practitioners were asked to rank the top four reasons for which they submitted samples (Figure 2), selecting from reasons related to within-herd monitoring, between-farm spread, and immunological considerations. From this survey, we can see that the reasons driving field efforts to sequence so many PRRSV viruses are related mainly to discriminating between previous and new PRRSV strains in the same farm or flow, determining possible sources of introduction in epidemiological investigations, and tracking the spread of novel and emerging genetic variants.

Figure 2. Summary of practitioners responses (n=92) when asked to rank the top four reasons for which samples are submitted for sequences, with 1 being the highest.

Immunological considerations were less important to practitioners, likely because of the challenge of predicting cross-protection or clinical impacts from ORF5 sequences. That being said, if sequence data were combined with robust meta-data often not available for non-agricultural pathogens, the sheer volume of sequences available for PRRSV-2 gives us a unique window to learn about viral evolution and the impact of genetic change.

This work was supported by the joint US-UK NIFA-NSF-NIH-BBSRC Ecology and Evolution of Infectious Disease award, the USDA Data Science for Food and Agricultural Systems, and the American Association of Swine Veterinarians.