Molecular characterization of cellular stress responses during coronavirus infection
Fung, To Sing
Date of Issue2015
School of Biological Sciences
Coronaviruses are important animal and human pathogens. In this study, two stress pathways – the unfolded protein response (UPR) and c-Jun N-terminal kinase (JNK) pathway are shown to be activated in cells infected with infectious bronchitis virus (IBV). The inositol requiring protein 1 (IRE1) branch of UPR protects infected cells from apoptosis by splicing the mRNA of X-box protein 1 (XBP1) and differentially modulating the activation of two kinases. The PKR-like ER protein kinase (PERK) branch of UPR promotes IBV-induced apoptosis by up-regulating C/EBP homologous protein (CHOP). JNK is phosphorylated by MKK7 during IBV infection, and it promotes apoptosis by modulating the level of B cell lymphoma-2 (Bcl2) family proteins. Moreover, IRE1 mediates autophagy induction whereas XBP1 and JNK contribute to the induction of pro-inflammatory cytokines (interleukin-8) and type-I interferon in the IBV-infected cells. Therefore, these stress pathways modulate critical cellular events and contribute to pathogenesis during coronavirus infection.