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. 2011 Aug 25;6(8):e22935. doi: 10.1371/journal.pone.0022935

Figure 7. IPNV induces ER stress-mediated host cell death cascade.

Figure 7

IPNV infection and early replication causes an ER stress response upon entry and the primary replication stage. Then, viral replication triggers an ER stress induction stage that includes: 1) activating ATF6 sensor that up-regulate chaperone protein GRP78; 2) PKR can phosphorylate the eIF2α; 3) PERK sensor is autophosphorylated, which can enhance eIF2α phosphorylation. Further, the PKR/PERK ER stress signal can induce CHOP up-regulation, which may correlate to Bcl-2 family members downregulation such as Bcl-2, Mcl-1 and Bcl-xL at early (0–6 h pi) and middle (6–12 h pi) replication stages. Finally, IPNV infection induce PKR/PERK-mediated downredulate Bcl-2 expression and MMP loss, which combined the death signals for triggering necrotic cell death at the mitochondrial dysfunction stage at middle and late (12–24 h pi) replication stages. Cell death could be modulated by: (a) VT to inhibition of GRP78 expression and (b) 2-AP to reduce PKR activation.