Contemporary United States PRRSV 1-4-4 L1C.5 isolate causes severe disease comparable to historic highly pathogenic PRRSV

Porcine reproductive and respiratory syndrome virus (PRRSV) is a major economic and animal health burden on the United States swine industry due to morbidity- and mortality-associated losses affecting all stages of pig production. Currently, a large proportion of losses are attributed to a highly virulent PRRSV strain, referred to here as L1C.5. A field-relevant contemporary L1C.5 isolate was characterized in pigs to assess disease kinetics in comparison to a moderately virulent PRRSV strain that emerged in the United States in the early 2000s (MN184), and a highly pathogenic PRRSV (HP-PRRSV) strain that devastated Asian swine industries beginning in 2006 (JXwn06). Weaned pigs were inoculated with PRRSV JXwn06, L1C.5, MN184, or mock inoculum and necropsied at 2, 6, and 10 days post-inoculation or as needed due to severe disease. Clinical metrics, viral loads, cytokine concentrations, antibody concentrations, and pathology were compared between groups to assess pathogenicity. JXwn06 and L1C.5 animals developed more severe disease that diverged from MN184 and mock animals. Disease dynamics were also highly similar between JXwn06 and L1C.5 groups. Results demonstrate that despite unique genetics, geographical origins, and dates of emergence, a contemporary United States-endemic PRRSV (L1C.5) can cause severe disease comparable to a HP-PRRSV (JXwn06) that devastated the Asian swine industry nearly two decades ago. Identifying the common features that contribute to increased virulence of diverse HP-PRRSV strains will be essential for tailoring better PRRSV control methods, especially for contemporary PRRSV strains that pose imminent threats to swine health in North America.