Porcine reproductive and respiratory syndrome virus infection activates NOD2–RIP2 signal pathway in MARC-145 cells

Nucleotide-binding oligomerization domains (NOD)-like receptors (NLRs) evolve as a group of germline-encoded receptors that detect cytosolic pathogen-associated molecular patterns. Porcine reproductive and respiratory syndrome virus (PRRSV) is an Arterivirus that has been devastating the swine industry worldwide. By examining the expression kinetics of ten selected NLRs, NOD2 and NLRP3 were found to be continuously up-regulated in PRRSV-infected MARC-145 cells during 48 h of post-infection. Further study revealed that PRRSV infection enhanced the expression and phosphorylation of RIP2. Knockdown of NOD2 and RIP2 by siRNA significantly decreased PRRSV-induced phosphorylation of NF-κB subunit p65, JNK, Erk and p38 MAPK, as well as the expression of IL-6, IL-8, TNF-α, and RANTES in MARC-145 cells. Moreover, increased expression of NOD2 and RIP2 mRNA were observed in alveolar macrophages isolated from PRRSV-challenged piglets at 3, 7 and 10 day post-challenge. Collectively, our results revealed that PRRSV infection activates NOD2–RIP2 signaling pathway to induce pro-inflammatory response.