Innate Response Window, Gene Networks and Molecular Markers for Improved Genetic Resistance to PRRSV Infection.

Porcine reproductive and respiratory syndrome (PRRS), caused by a small RNA virus (PRRSV) has been devastating the pig industry worldwide for more than 25 years.  Due to the high-mutation rate and immune-suppressive capability of PRRSV, both modified live-attenuated vaccines and inactivated vaccines cannot efficiently prevent respiratory infection and pig-to-pig transmission of the virus.  As such, a USDA coordinated agricultural project was funded to develop integrated strategies for controlling and reducing the impact of PRRS.  In the present study, we used a nursery pig model, a microphage in vitro challenge model and a pathway-based approach to characterize the innate response window, gene networks and molecular markers associated with genetic resistance to PRRSV infection.  Comparison of effects of modeled virus growth rates at different time points on both virus load and body weight trends during a 42 day period of PRRSV infection revealed evidence that an innate response window might exist from 11 to 14 days post infection.  Transcriptome analysis on microphages challenged with PRRSV identified 699 differentially expressed genes. Among them, 573 were assigned to six biological systems, 60 functional categories and 504 pathways.   Genetic markers are currently being developed in interferon induced proteins, antigen processing, autophagosome formation and hibernation related protein genes with potential involvements in innate resistance to PRRSV infection.  In brief, our findings should provide new insights into understanding the pathogenesis of PRRS and facilitate developing new approaches to prevent or diagnose PRRSV. This work was supported by the USDA NIFA PRRS CAP, #2008-55620-19132.