The epidemiological and evolutionary dynamics of porcine reproductive and respiratory syndrome (PRRS) virus

Abstract

Porcine reproductive and respiratory syndrome virus (PRRSV), a member of the family Arteriviridae, encompasses two genetically and antigenically distinct genotypes (type 1 and type 2 PRRSVs). To date, one or both types of PRRSV have been detected in almost all swine-producing countries. In addition, the recent emergence of a highly pathogenic type 2 PRRSV with high mobility and mortality in China has placed neighboring countries at risk. Because understanding the spatial-temporal transmission patterns and methods of pathogen genetic variation is important for effective prevention and vaccine development, the epidemiological and evolutionary dynamics of PRRSV were explored. The first part of this study focused on the molecular epidemiology of type 1 PRRSV worldwide. Throughout the Bayesian phylogeographical analysis of a large ORF5 dataset collected from 1991 to 2012, details of the diffusion histories of type 1 PRRSV across pig-producing countries were uncovered. Following that phylogeographical footprint, it was found that type 1 PRRSV tended to cluster by geographical locations to form distinctive population structures. In each population, the evolution of the ORF5 gene was best described by a non-homogeneous process. In the second part of this study, the question of how type 1 PRRSV had evolved upon its introduction to the pig populations on a country level was addressed by focusing on the long-term circulation of the virus in Korea. The maximum likelihood phylogenetic analysis performed on large, worldwide ORF5 sequences strongly suggested no further introduction of genetically novel type 1 PRRSV into Korean pig farms, with the identification of only two clusters in circulation to date. Utilizing a codon-based extension of the Bayesian relaxed clock model, and the novel Bayesian birth-death skyline plot, it was revealed that genetically different clusters of Korean type 1 PRRSV experienced a unique evolutionary and epidemiological dynamics. Finally, this study investigated and compared the evolutionary dynamics between the highly pathogenic clade and the typical clade of type 2 PRRSV. After applying a codon-based extension of the Bayesian relaxed clock model and the fixed effects maximum likelihood method to all of known structural envelopeprotein-coding genes, we were able to demonstrate that the highly pathogenic clade did not display rapid evolutionary dynamics compared with typical type 2 PRRSV. In contrast, several structural genes and codons had been found to evolve in qualitatively different manners and were differentially selected between the typical clade and the highly pathogenic clade of type 2 PRRSV. In conclusion, this study successfully reconstructs the global transmission histories, the evolutionary and epidemiological dynamics at a country level of type 1 PRRSV. Extended to the genome-scale analysis of evolutionary dynamics, several structural genes and codons have been found to contribute to the differential evolutionary dynamics between the typical clade and the highly pathogenic clade of type 2 PRRSV. The detailed knowledge about the evolutionary and epidemiological dynamics of PRRSV presented in this study yields valuable information in vaccine development, such as which virus strain should be selected for vaccination against type 1 PRRSV in Korea, and which genes should be considered in the application of molecular-based approaches for developing more effective vaccines.