Fig. 4.

Involvement of UPR in innate immune response during coronavirus infection. The PKR/PERK mediated eIF2α phosphorylation leads to translation attenuation and lower level of IκBα synthesis. On the other hand, IRE1 recruits TRAF2 and activates IKK to phosphorylate IκBα, promoting its ubiquitination and degradation. The outcome is a lower protein level of IκBα, releasing NF-κB for activation of type-I interferons and/or cytokines. The PERK branch also activates NF-κB by up-regulation of CHOP, which forms heterodimer with C/EBPβ and prevent it from activating PPARγ that suppresses NF-κB activation. The MAP kinases p38 and JNK activate AP-1 and promote cytokine production. Under ER stress, JNK is phosphorylated by IRE1/TRAF2 complex, while ATF3 has been shown to induce DUSP1 that de-phosphorylates p38. Several proteins, such as GADD34 or the spliced form of XBP1, have been shown to cross-talk with the innate immune signaling. Refer to text for detailed description.