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Title:   Author  item
                                            Loving, Crystalitem
                                            Brockmeier, Susanitem
                                            Baker, Amyitem
                                            Lager, Kellyitem
                                            Sacco, Randy
  Submitted to: Viral Immunology
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 5/15/2008
                                    Publication  Date: 9/5/2008
                                    Citation: Loving, C.L., Brockmeier, S.L., Vincent, A.L., Lager, K.M., Sacco, R.E. 2008. Differences in clinical disease and immune response of pigs challenged with a high-dose versus low-dose inoculum of porcine reproductive and respiratory syndrome virus. Viral Immunology. 21(3):315-325.Interpretive Summary: Porcine reproductive and respiratory syndrome virus (PRRSV) continues to be an economically important infectious disease of swine.  The current study was completed to understand how the amount of virus a pig is exposed to at the time of infection can affect the course of disease.  Animals challenged with a low dose of PRRSV did not become as sick as those challenged with a high dose, but the amount of virus detected in animals from the two groups was not different.  Thus,  the amount of virus in the serum was not predictive of survival. Overall, pigs exposed to a high dose of the virus exhibited enhanced disease whereas pigs exposed to a low dose of the virus were able to mount an immune response that led to clearance of the virus.
                                Technical Abstract: Porcine reproductive and respiratory syndrome virus (PRRSV) continues to be an economically important infectious disease of swine.  Mechanisms governing activation of the innate immune response to PRRSV remain to be elucidated.  Virulence differences observed between PRRSV isolates have been attributed to replication ability in vivo, though immunogenic differences likely contribute to virulence also. The current study utilized a single PRRSV isolate given at two different challenge doses to investigate the effect of viral replication and load on immune responses, including type I interferon activation.  Body temperature, viral load, antibody levels, cellular infiltration into pulmonary tissue, and the interferon response were measured in animals receiving either a low (102 CCID50) or high (106 CCID50) dose inoculum to understand the role of challenge dose in acute immune responses. Initial PRRSV dose did not correlate to serum levels of PRRSV vRNA, nor antibody titers, during the acute stage of infection (day 2 to 12 PI), but did have an effect on the immune response and mortality. Type I interferon responses, measured by transcriptional changes in IFN-ß, IFN-a, Mx, and PKR, were uniquely different when assessed relative to viral dose or cell type, but no overall trend existed to discern responses based on challenge dose. Serum IFN-' levels correlated to serum viral RNA load, though differences between challenge groups were not demonstrated until day 19 PI. Overall, between day 2 and 12 PI, vRNA load was not significantly different between pigs challenged with a low or high dose of PRRSV.  Animals receiving high dose inoculum were viremic longer and eventually succumbed to respiratory disease. IFN-' may play a role in PRRSV pathogenesis, as serum levels increased significantly in pigs challenged with the high dose of PRRSV.


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