| First Author | Peña J | Year | 2011 |
| Journal | J Biol Chem | Volume | 286 |
| Issue | 16 | Pages | 14226-36 |
| PubMed ID | 21385877 | Mgi Jnum | J:171119 |
| Mgi Id | MGI:4948765 | Doi | 10.1074/jbc.M111.222703 |
| Citation | Pena J, et al. (2011) Dengue Virus Modulates the Unfolded Protein Response in a Time-dependent Manner. J Biol Chem 286(16):14226-36 |
| abstractText | Flaviviruses, such as dengue virus (DENV), depend on the host endoplasmic reticulum for translation, replication, and packaging of their genomes. Here we report that DENV-2 infection modulates the unfolded protein response in a time-dependent manner. We show that early DENV-2 infection triggers and then suppresses PERK-mediated eIF2alpha phosphorylation and that in mid and late DENV-2 infection, the IRE1-XBP1 and ATF6 pathways are activated, respectively. Activation of IRE1-XBP1 correlated with induction of downstream targets GRP78, CHOP, and GADD34. Furthermore, induction of CHOP did not induce apoptotic markers, such as suppression of anti-apoptotic protein Bcl-2, activation of caspase-9 or caspase-3, and cleavage of poly(ADP-ribose) polymerase. Finally, we show that DENV-2 replication is affected in PERK(-/-) and IRE1(-/-) mouse embryo fibroblasts when compared with wild-type mouse embryo fibroblasts. These results demonstrate that time-dependent activation of the unfolded protein response by DENV-2 can override inhibition of translation, prevent apoptosis, and prolong the viral life cycle. |
