Involvement of unfolded protein response, p53 and Akt in modulation of porcine reproductive and respiratory syndrome virus-mediated JNK activation

Our previous study has shown that activation of JNK plays a critical role in Porcine reproductive and respiratory syndrome virus (PRRSV)-mediated apoptosis. In this follow-up study, we further investigated the mechanisms involved in modulation of PRRSV-mediated JNK activation and apoptosis. We found that unfolded protein response (UPR) was induced in response to PRRSV infection which in turn triggered JNK activation and apoptosis. We also found that p53 and Akt were activated at the early stage of infection and functioned as negative regulator of JNK activation to counteract the PRRSV-mediated apoptosis. Furthermore, induction of UPR, p53 and Akt was not only involved in modulation of PRRSV-mediated apoptosis, but also contributed to the virus replication. Our findings indicated that multiple signaling pathways were involved in modulation of PRRSV-mediated apoptosis of the host cells via regulating JNK signaling pathway and provided novel insights into understanding the mechanisms of pathogenesis of PRRSV infection. (c) 2013 Elsevier Inc. All rights reserved.