#17-160

Complete

Date Full Report Received

03/13/2019

Date Abstract Report Received

03/13/2019

Investigation

Institution:
Primary Investigator:

In 2016 our lab showed that genetically edited pigs lacking expression of the CD163 protein on macrophages fail to support the replication of PRRSV. This was the first clear demonstration of how genetic modification can be used to prevent PRRS. This technology has since been used to demonstrate resistance to other swine diseases. Since CD163 is required for scavenging excess hemoglobin from the blood and participates in the regulation of inflammation, deletion of the entire CD163 protein has important negative consequences for the pig. Additional work, funded by the NPB and USDA NIFA, is directed at refining the genetic modification of CD163 to identify the smallest modifications in CD163 that confer resistance to PRRS without affecting other important functions. Since PRRSV undergoes rapid mutations in the field, the goal of this research is to determine if PRRSV can adapt successfully to different modifications in CD163; and if so, where the mutations for the adapted viruses are located within the surface genes of the viral genome. The experimental approach was to repeatedly passage PRRSV on HEK cell lines expressing mutations in SRCR domain 5 of CD613. Domain 5 is one of the critical regions required for PRRSV infection. The results showed that several mutations supported virus infection to some level. The repeated passage of PRRSV resulted in the appearance of mutations in the ORF6 protein. Overall, the results indicate that PRRSV remains relatively stable when passaged on cells possessing mutations in CD163.