title: 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.
abstract: 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.
authors.affiliation: State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing 100193, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Hou
authors.forename: Lianghai
authors.initials: L
authors.lastname: Wang
authors.forename: Weiyong
authors.initials: W
authors.lastname: He
authors.forename: Hexiao
authors.initials: H
authors.lastname: Zhang
authors.forename: Wen-hai
authors.initials: WH
authors.lastname: Feng
mesh_terms: D000818:Animals; D015536:Down-Regulation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000235:genetics / Q000378:metabolism; D020935:MAP Kinase Signaling System; D010766:Phosphorylation; D011070:Poly I-C / Q000378:metabolism*; D019318:Porcine Reproductive and Respiratory Syndrome / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D019316:Porcine respiratory and reproductive syndrome virus / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
chemical_list: D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D048049:Extracellular Signal-Regulated MAP Kinases; D011070:Poly I-C