Fig. 4.

Schematic showing the interaction between E.R. stress, UPR, and antioxidant system in response to M-CoV infection. Graphical abstract summarizes our new findings that DJ-1 under the influence of XBP-1 can regulate the reactive oxygen species (ROS) imbalance in virus-infected CNS cells. The assembly of the individual structural proteins into a virion induces E.R. stress and UPR. E.R. stress, UPR, and mitochondria in virus-infected cells tend to generate ROS in large quantities. On the contrary, the host cell system generates XBP-1 in response to E.R. stress and UPR. XBP-1 binds to the DJ-1 promoter and increases the expression of DJ-1. DJ-1, in turn, up regulates Nrf2 and facilitates its translocation to the nucleus. The transcription factor Nrf2 binds to the antioxidant responsive element (ARE) in the promoter region and induces the expression of Nrf2 dependent antioxidant genes HMOX-1, Nqo1, Catalase, and HSF1. These antioxidant genes play a significant role in quenching the ROS and protect the cell from ROS mediated cellular damage and death.