Phylodynamic analysis of porcine reproductive and respiratory syndrome virus (PRRSV) in Italy: Action of selective pressures and interactions between different clades

• Definition of a database comprising all ORF5 sequences of Italian PRRSV strains.
• Analysis of genetic variability of PRRSV Italian strains between 1993 and 2012.
• Phylogenetic analysis to contextualize Italian sequences within the world landscape.
• Analysis of recombination, population dynamic, selective pressures and glycosylation.
• Investigation of interactions between circulating viral clades and with vaccines.

Porcine reproductive and respiratory syndrome (PRRS) is the most relevant and challenging infectious disease to affect swine breeding. Despite this, several aspects of the virus’ evolution and virus–host interaction are still poorly understood and largely based on knowledge obtained through in vitro or in vivo experimental infections. Due to peculiar experimental conditions, our understanding is often contradictory and difficult to infer with respect to actual field conditions. Our phylodynamic study, based on ORF5 sequences of 141 samples collected in Italy from 1993 to 2012, explores different aspects of PRRSV epidemiology, evolution, and virus–host interaction. Two major clades, belonging to Type 1 subtype 1, were demonstrated to co-circulate while harboring a relevant intra- and inter-clade genetic diversity. Most Recent Common Ancestor (MRCA), evolution rates, and population dynamics were estimated using a serial coalescent-based approach, and different demographic histories were reconstructed for the two clades. Analysis of selective pressure revealed that sites subjected to diversifying selection were mainly located in the region of glycoprotein 5 (GP5) exposed to the host environment. Similarly, the vast majority of strains were highly glycosylated, confirming the proposed protective role of the glycan shield against the humoral immune response. Overall, our study reports both interactions among the viral populations as well as between virus and host, and their relevance in shaping viral evolution: different population dynamics over time seem to reflect a competition between clades. Some evidence argues in favor of the role of immune pressure in affecting GP5 evolution, including frequent changes in the region exposed to the host immune response, and preserving glycosylation profiles that can hamper humoral immunity.