Robinson, Sally2015-11-062015-11-062015-05https://hdl.handle.net/11299/175315University of Minnesota Ph.D. dissertation. 2015. Major: Comparative and Molecular Biosciences. Advisor: Michael Murtaugh. 1 computer file (PDF); 169 pages.Porcine reproductive and respiratory virus (PRRSV) is a rapidly evolving and diverse RNA virus that causes significant disease to swine populations globally. There are no specific treatments for PRRSV; biosecurity measures and immunization are the mainstays of PRRSV prevention and control. Although immunization plays a critical role in reducing disease and stabilizing virus-endemic herds, vaccines provide incomplete and unpredictable cross-protection against the diversity of PRRSV strains. A limitation for improving immunization strategies is that mechanisms responsible for immunity against PRRSV and correlates of cross-protection are poorly understood. The objective of this dissertation was to re-evaluate aspects of PRRSV immunity in light of contemporary information for novel clues to identify mechanisms of protection. The approach was to investigate the role of recently discovered PRRSV protein ORF5a in immunity, and to re-evaluate the role of neutralizing antibodies in PRRSV cross-protection. The findings herein demonstrate that ORF5a protein is not important for immune protection against PRRSV but the maintenance of ORF5a in fine evolutionary balance with the GP5 variable glycosylation region suggests it plays a critical role in the virus life cycle. High levels of broadly-neutralizing antibodies to PRRSV were identified from sows in typical commercial settings. Neutralizing antibodies isolated from sows provided cross-protection to naïve animals against diverse strains of PRRSV. This information provides a basis for renewed investigation into the mechanisms of neutralizing antibody-mediated protection against PRRSV and strategies for induction of broadly-neutralizing antibodies. Improved understanding of immune mechanisms to PRRSV will enable more effective control, prevention and ultimately, elimination of the virus.encross-protectionimmune protectionneutralizing antibodiesporcinePRRSVThesis or Dissertation