Working Paper Article Version 1 This version is not peer-reviewed

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

Version 1 : Received: 12 February 2021 / Approved: 16 February 2021 / Online: 16 February 2021 (13:48:02 CET)

A peer-reviewed article of this Preprint also exists.

Turpin, J.; El-Safadi, D.; Lebeau, G.; Frumence, E.; Desprès, P.; Viranaïcken, W.; Krejbich-Trotot, P. CHOP Pro-Apoptotic Transcriptional Program in Response to ER Stress is Hacked by Zika Virus. Int. J. Mol. Sci. 2021, 22, 3750. Turpin, J.; El-Safadi, D.; Lebeau, G.; Frumence, E.; Desprès, P.; Viranaïcken, W.; Krejbich-Trotot, P. CHOP Pro-Apoptotic Transcriptional Program in Response to ER Stress is Hacked by Zika Virus. Int. J. Mol. Sci. 2021, 22, 3750.

Journal reference: Int. J. Mol. Sci. 2021, 22, 3750
DOI: 10.3390/ijms22073750

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 newborns. 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 signaling 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.

Subject Areas

Zika virus; ER stress; unfolded protein response; apoptosis; CHOP

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