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CHOP Pro-Apoptotic Transcriptional Program in Response to ER Stress Is Hacked by Zika Virus

Abstract : Zika virus (ZIKV) is an emerging mosquito-borne flavivirus considered as a threat to human health due to large epidemics and serious clinical outcomes such as microcephaly in new-borns. Like all flaviviruses, ZIKV relies on the cellular machinery to complete its viral cycle, with the endoplasmic reticulum (ER) being the critical site of viral replication factories. The sudden high protein load in the ER induces an ER stress to which the cell responds with an appropriate unfolded protein response (UPR) in an attempt to restore its disturbed homeostasis. When the restoration fails, the cell signalling leads to a programmed cell death by apoptosis with the upregulation of the UPR-induced C/EBP homologous protein (CHOP) which acts as the main trigger for this fatal outcome. Our previous studies have shown the ability of ZIKV to manipulate various cellular responses in order to optimize virus production. ZIKV is able to delay apoptosis to its benefit and although ER stress is induced, the UPR is not complete. Here we discovered that ZIKV impairs the expression of CHOP/DDIT3, the main factor responsible of ER-stress driven apoptosis. Surprisingly, the mechanism does not take place at the transcriptional level but at the translational level.
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https://hal.univ-reunion.fr/hal-03702919
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Submitted on : Thursday, June 23, 2022 - 2:45:05 PM
Last modification on : Monday, June 27, 2022 - 2:31:49 PM

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ijms-22-03750-v2.pdf
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Jonathan Turpin, Daed El-Safadi, Grégorie Lebeau, Etienne Frumence, Philippe Desprès, et al.. CHOP Pro-Apoptotic Transcriptional Program in Response to ER Stress Is Hacked by Zika Virus. International Journal of Molecular Sciences, MDPI, 2021, 22, pp.3750. ⟨10.3390/ijms22073750⟩. ⟨hal-03702919⟩

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