The PRRSV-2 Saga: Evolutionary and Epidemiological Dynamics of Porcine Reproductive and Respiratory Syndrome Virus 2 in the United States

Abstract

Porcine reproductive and respiratory syndrome (PRRS) has inflicted substantial economic losses on the US swine industry over the past three decades, driven by the main etiological agent, PRRSV-2, which continuously evolves and spreads despite control efforts. Enhancing disease control measures necessitates an understanding of evolutionary dynamics of PRRSV. By leveraging virus genetic data and bioinformatics tools, this dissertation aims to unravel how PRRSV-2 has adapted, persisted, and disseminated within the U.S. Chapter 1 provides a background of the disease, the virus itself, and the existing knowledge gaps. Chapter 2 employs nationwide PRRSV-2 genetic and geographic data to uncover the patterns of disease spread and the dynamics of the virus population within the U.S. In Chapter 3, we conduct an in-depth investigation into between-farm transmission of an emerging PRRSV-2 sub-lineage within a specific, swine-dense region, using genetic and animal movement data. Chapter 4 utilizes data from the largest active PRRS monitoring program in the U.S. to forecast the potential emerging variants. Finally, in Chapter 5, we pinpoint the origin of a novel PRRSV-2 variant through an advanced analysis of whole-genome sequences.Chapter 2 revealed a cyclical pattern of sub-lineages contributing to the overall PRRSV-2 population and a shift across time in major hotspots for inter-regional spread. In Chapter 3, we narrow our focus to intra-regional spread by applying molecular epidemiological tools to construct farm-to-farm transmission networks for an emerging PRRSV-2 sub-lineage. These networks allowed us to examine factors contributing to between-farm spread and highlighted the significance of live animal movement, while recognizing that most transmission events remained unexplained. Both Chapters 2 and 3 characterize the periodic emergence of novel genetic variants of PRRSV-2, and anticipating such emergence events could aid in more strategic disease control. Chapter 4 demonstrated the utility of phylogenetic branching patterns and putative antigenic differences as early indicators of variant emergence. Finally, in Chapter 5, we expand the discussion of variant emergence from the ORF5 gene to the whole genome perspective. Analysis of whole-genome sequences unveiled a recombinant ancestor for an emerging variant of concern and emphasized the role of genomic recombination in PRRSV-2 evolution. Ultimately, our findings address novel insights into PRRSV-2 evolution and epidemiology at various geographic scales, providing beneficial guidance for targeted and early-response PRRS mitigation strategies in the U.S.