Highly pathogenic porcine reproductive and respiratory syndrome virus impairs LPS- and poly(I:C)-stimulated tumor necrosis factor-alpha release by inhibiting ERK signaling pathway.

Atypical porcine reproductive and respiratory syndrome (PRRS) characterized by high morbidity and mortality emerged in China in 2006. The causative agent was confirmed to be a highly pathogenic PRRS virus (HP-PRRSV). However, the pathogenesis of HP-PRRSV is still uncertain. Here, the ability of the highly pathogenic strains (HV and JX) to induce tumor necrosis factor alpha (TNF-α) was studied. Our results showed that HV and JX were weaker inducers of TNF-α than the conventional strain CH-1a. Moreover, HV infection was demonstrated to suppress extracellular signal-regulated kinase (ERK) phosphorylation at the early time points. Pharmacologic inhibition or activation of ERK revealed that TNF-α production in HV-infected macrophages was associated with the activation status of ERK. Furthermore, HV- and JX-infection could potently impair lipopolysaccharide (LPS)- and poly(I:C)-stimulated TNF-α release in a dose dependent manner whereas synergistic effects were observed at mRNA level. The observation suggested the involvement of posttranslational impact of HP-PRRSV on TNF-α production, which might be attributed to the reduced ERK1/2 phosphorylation in response to toll-like receptor (TLR)-ligation. Taken together, our results indicated that HP-PRRSV infection could impair TNF-α production by inhibiting ERK signaling pathway, which might partially contribute to the pathogenesis of HP-PRRSV.