Regulatory role of ASK1 in porcine circovirus type 2-induced apoptosis.

Porcine circovirus type 2 (PCV2), a major causative agent of postweaning multisystemic wasting syndrome which is an emerging and important swine disease, can induce apoptotic responses in vitro and in vivo. However, the molecular mechanism of PCV2-induced apoptosis is not well understood. Apoptosis signal-regulating kinase 1 (ASK1), serves as an upstream enzyme that activates the JNK and p38 MAPK pathways, has been shown to play a target role in the regulation of apoptosis. Here, we showed that PCV2 infection induced ASK1 phosphorylation which preceded activation of JNK1/2 and p38 signaling in the cultured cells, and that the phosphatidylinostol 3-kinase (PI3K)/Akt signaling triggered by PCV2 infection limited the extent of JNK1/2 and p38 activation and thereby apoptotic cell death. Furthermore, inhibition of JNK and p38 activation is associated with PI3K-dependent negative-regulation of ASK1 in the PCV2-infected cells. These results indicate an important regulatory role of ASK1 in PCV2-induced apoptotic responses.