Porcine circovirus type 2 infection activates NF-κB pathway and cellular inflammatory responses through circPDCD4/miR-21/PDCD4 axis in porcine kidney 15 cell

Porcine circovirus type 2 (PCV2) causes postweaning multisystemic wasting syndrome (PMWS) as well as other PCV-associated diseases (PCVADs), which seriously affect the development of the swine industry. The association between aberrant expression of microRNA-21 (miR-21) and the pathogenesis of inflammatory diseases is already known. Also, our previous study showed elevated ssc-miR-21-5p (miR-21) levels in PCV2-infected porcine kidney 15 (PK-15) cells. However, the functional expression of miR-21 in PCV2 infection is unknown. Here, we found that the miR-21 levels were substantially upregulated in PCV2-infected cells, while the expression of PDCD4 and a PDCD4-derived circRNA (circPDCD4) were downregulated compared with the noninfected cells. The results of RNA immunoprecipitation and dual-luciferase reporter (DLR) assay revealed that circPDCD4 acted as a miR-21 sponge and PDCD4 was a miR-21 target. Functionally, we found that miR-21 overexpression induced the NF-κB pathway along with inflammation in cells exposed to PCV2. Further, the overexpression of PDCD4 or circPDCD4 downregulated miR-21 levels and subsequently, attenuated the miR-21-induced activation of inflammation and the NF-κB pathway. Thus, PCV2 activated the NF-κB pathway and cellular inflammatory responses through regulating circPDCD4, miR-21, and PDCD4 in PK-15 cells.