Repeat offenders: PRRSV-2 clinical re-breaks from a whole genome perspective.

Abstract

Listen

Translate article

Clinical re-breaks of PRRSV on sow farms are a frustrating reality for producers and practitioners. The underlying mechanisms allowing for a single viral variant to persist and cause repeated clinical outbreaks within a herd that should have strong immunity, through recent exposure to a highly similar genetic variant (≥%97 homology), are poorly understood. This study systematically identified clinical re-breaks on sow farms and performed whole genome sequencing on viral isolates available from each outbreak event to evaluate the hypothesis that such re-breaks may be associated with evolution on glycoprotein ectodomains. Pairwise comparisons between re-break isolates revealed multiple amino acid sites in structural proteins that frequently differed between re-break pairs. For sites identified on GP5, several sites were found to be changed in a higher proportion of re-breaks than expected from background variability. Intriguingly, 4 of 13 re-break events had no changes on GP5 but numerous changes in other structural protein ectodomains; GP2, E, GP3, and GP4 all contained several sites that were substituted in a high proportion of rebreak pairs, highlighting the multigenic nature of immune evasion. Across all structural proteins, most sites were located on ectodomains (15/22; 68 %). Several GP5 sites (6/8; 75 %) have been associated with escape from antibody neutralization in in vivo and in vitro experiments. To conclude, identification of suspected immune escape events from production and surveillance data resulted in detection of crucial amino acid positions on structural proteins that potentially underly antigenic diversity. Such micro-evolutionary change could result in escape from antibody neutralization, complicating interventions such as herd closures and leading to persistence of clinical outbreaks on sow farms.