Figure 9

DENV2-induced autophagy is ER stress-UPR dependent, involving PERK-eIF2α-ATF4 and IRE1α-JNK-BECN1 pathways. DENV2 infection temporally modulates UPR in the order of PERK, IRE1 and ATF6 in human cells. PERK-ATF4-ATG12 and IRE1α-JNK are the two major signaling pathways participating in DENV2-induced autophagy and viral replication. The phosphorylated JNK further activates the downstream molecule Bcl-2, and BECN1 then dissociates from Bcl-2/BECN1 complex when Bcl-2 was activated, which is one of the molecules responsible for autophagy induction and promotes viral replication. However, IRE1α-XBP1 pathway shows no impact on DENV2-induced autophagy and viral replication but involved in regulating IL-8 and TNFα production during DENV2 infection. Significance was defined as *p < 0.05; **p < 0.01 and ***p < 0.001.