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• W2119707827 abstract "ABSTRACT West Nile virus strain Kunjin (WNV KUN ) is an enveloped, positive-sense RNA virus within the virus family Flaviviridae . Many flaviviruses have been shown to manipulate multiple signaling pathways, including autophagic, innate immune, and stress responses, in order to benefit replication. In particular, we have demonstrated that WNV KUN regulates the unfolded protein response (UPR), skewing the downstream effectors toward chaperone expression and Xbp-1 activation while preventing PERK-mediated translation attenuation and C/EBP homologous protein (CHOP) upregulation. WNV KUN -regulated UPR signaling can then be hijacked in order to affect type I interferon (IFN) responses, preventing IFN-mediated STAT1 phosphorylation and nuclear translocation. To extend our previous observations, we aimed to investigate the contribution of ATF6- and IRE1-mediated signaling during WNV KUN replication and how the two sensors contribute to the inhibition of IFN signaling. ATF6-deficient cells infected with WNV KUN showed decreased protein and virion production. These cells also demonstrated increased eIF2α phosphorylation and CHOP transcription, absent in infected matched control cells. Thus, we propose that in the absence of ATF6, WNV KUN is incapable of manipulating the PERK-mediated response to infection. In contrast, infection of IRE1 −/− knockout cells showed no discernible differences compared to IRE1 +/+ cells. However, both ATF6 and IRE1 were required for WNV KUN -induced inhibition of STAT1 phosphorylation. We suggest that the combination of abhorrent UPR signaling, promotion of cell death, and increased innate immune responses contributes to the replication defects in ATF6-deficient cells, thus demonstrating the dual importance of ATF6 in maintaining cell viability and modulating immune responses during WNV KUN infection." @default.
• W2119707827 created "2016-06-24" @default.
• W2119707827 creator A5074756255 @default.
• W2119707827 creator A5081178927 @default.
• W2119707827 date "2013-02-15" @default.
• W2119707827 modified "2023-09-26" @default.
• W2119707827 title "ATF6 Signaling Is Required for Efficient West Nile Virus Replication by Promoting Cell Survival and Inhibition of Innate Immune Responses" @default.
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• W2119707827 doi "https://doi.org/10.1128/jvi.02097-12" @default.
• W2119707827 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3571479" @default.
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