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Version 1
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Herpesviruses and the Unfolded Protein Response
Version 1
: Received: 3 December 2019 / Approved: 4 December 2019 / Online: 4 December 2019 (04:38:02 CET)
A peer-reviewed article of this Preprint also exists.
Johnston, B.P.; McCormick, C. Herpesviruses and the Unfolded Protein Response. Viruses 2020, 12, 17. Johnston, B.P.; McCormick, C. Herpesviruses and the Unfolded Protein Response. Viruses 2020, 12, 17.
Abstract
Herpesviruses usurp cellular stress responses to avoid immune detection while simultaneously promoting viral replication and spread. The unfolded protein response (UPR) is an evolutionarily conserved stress response that is activated when the protein load in the ER saturates its chaperone folding capacity causing an accrual of misfolded proteins. Through translational and transcriptional reprogramming, the UPR aims to restore protein homeostasis; however, if this fails the cell undergoes apoptosis. It is commonly thought that many enveloped viruses, including herpesviruses, may activate the UPR due to saturation of the ER with nascent glycoproteins and thus these viruses may have evolved mechanisms to evade the potentially negative effects of UPR signaling. Over the past fifteen years there has been considerable effort to provide evidence that different viruses may reprogram the UPR to promote viral replication. Here we provide an overview of the molecular events of UPR activation, signaling and transcriptional outputs, and highlight key findings that demonstrate that the UPR is an important cellular stress response that herpesviruses have hijacked to facilitate persistent infection.
Keywords
unfolded protein response (UPR); integrated stress response (ISR); ATF6; IRE1; XBP1; PERK; ATF4; GADD34; herpesvirus; Kaposi’s sarcoma-associated herpesvirus (KSHV); cytomegalovirus (CMV); herpes simplex virus (HSV)
Subject
Biology and Life Sciences, Virology
Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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