#17-171

Complete

Date Full Report Received

11/26/2019

Date Abstract Report Received

11/26/2019

Investigation

Institution:
Primary Investigator:

In the majority of cases involving new PRRSV isolates, outbreak severity initially is tremendous, then decreases over time as herd immunity and biosecurity is managed to reduce and prevent disease. Challenge studies have shown that commercial vaccines significantly improve outcomes compared to infection of naïve animals. PRRS viruses that break in solidly immune, vaccinated herds as if they were naïve are very difficult to manage and threaten economic swine production. An unusually aggressive family of viruses characterized by a 1-7-4 RFLP appeared in January 2014 and within 15 months was linked to severe outbreaks in well managed herds. These viruses are markedly different from other contemporary field viruses in their ability to spread rapidly and cause severe disease in immune (endemic) herds.
In this study we focused on examining the differences between historical and contemporary isolates of varying virulence levels to identify possible reasons for the unusually high virulence of contemporary viruses including the 1-7-4 RFLP viruses. The objectives of this project were to 1) examine serum neutralization titers between animals exposed to different viruses, 2) characterize the growth characteristics of contemporary virulent viruses, 3) discover unique genomic features that may be involved in viral virulence, and 4) examine new methods for classification of PRRSV isolates that may more effectively predict potential highly virulent viral strains. First, we determined that the contemporary 1-7-4 RFLP viruses were sufficiently antigenically distinct from vaccine that they evaded the vaccine-induced immune response, thus vaccine did not induce any protection against these viruses. However, once an animal was infected with a contemporary virus, they were protected against infection by other contemporary strains. Secondly, the growth characteristics of contemporary strains were compared to that of historical strains to try and explain why these contemporary strains are so virulent, but no significant growth advantages were observed. Next, genome sequences from contemporary and historic viruses of various virulence were compared to identify possible virulence genes or targets for diagnostics or vaccination. Interestingly, 6 regions of the genome were observed to contain putative proteins that were conserved across all or most of the viral genomes examined, suggesting more proteins may be involved in viral replication than previously known. Surprisingly, comparing high vs low virulence viral genomes identified 3 regions predicting different protein products depending upon virulence of the virus. In one region, a protein was predicted to be present in low virulence viruses, but was not observed in any medium or high virulence viruses, thus suggesting it is involved in maintaining low virulence and deserves further study. Finally, viral genome sequences were examined using a variety of clustering methods and were compared with RFLP-typing to try and differentiate highly virulent strains from lower or non-virulent viruses. Unfortunately, no magic method was identified to differentiate viral virulence. However, ORF5 or whole genome clustering did give better results than that of RFLP-typing to differentiate low or non-virulent strains from virulent strains. Overall, this research suggests that contemporary viruses differ enough from vaccine strains that little or no protection against contemporary strains is obtained from these vaccines. However, contemporary strains are able to protect against infection by other contemporary viruses, suggesting that vaccine derived from contemporary strains would be protective. The identification of possible regions involved in virulence may allow for quicker vaccine development. Identification of new viral clusters using ORF5 sequencing will help identify new strains that may be able to evade vaccine-induced immunity, thus identifying the need for updated vaccines.
For more information please contact Dr. Cheryl Dvorak at the Veterinary and Biomedical Sciences Department at the University of Minnesota, email: dvora013@umn.edu
Key Findings:
• Contemporary 1-7-4 RFLP viruses evade vaccine-induced immunity.
• Antibodies induced by infection of contemporary viruses protects against infection by other contemporary viruses.
• Contemporary viruses do not seem to have a growth advantage over historical strains, but rather have evolved to evade vaccine-induced protection.
• Three regions of the genome were identified that encode putative virulence factors that may enhance vaccine development.
• Clustering by ORF5 or whole genome sequence along with neutralizing antibody assays can be used to determine when new PRRSV strains are likely to evade vaccine-induced immune responses.