Herpesviruses and the Unfolded Protein Response

• Published in: Viruses Vol. 12; no. 1; p. 17
• Main Authors: Johnston, Benjamin P, McCormick, Craig
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 21-12-2019; MDPI
• Subjects: Activating Transcription Factor 6 - genetics; Activating Transcription Factor 6 - metabolism; Animals; Apoptosis; Autophagy; Biosynthesis; Cellular stress response; Disease Susceptibility; Endoplasmic reticulum; Herpesviridae - classification; Herpesviridae - physiology; Herpesviridae Infections - metabolism; Herpesviridae Infections - virology; Homeostasis; Host-Pathogen Interactions; Humans; Immunosurveillance; Intracellular Membranes - metabolism; Kaposis sarcoma; Kinases; Mammals; Phosphatase; Phosphorylation; Protein folding; Protein synthesis; Proteolysis; Replication; Review; Sensors; Transcription activation; Transcription factors; Translations; Unfolded Protein Response; GADD34; XBP1; Kaposi’s sarcoma-associated herpesvirus (KSHV); herpesvirus; unfolded protein response (UPR); IRE1; integrated stress response (ISR); PERK; cytomegalovirus (CMV); ATF6; herpes simplex virus (HSV); ATF4
• ISSN: 1999-4915; 1999-4915
• DOI: 10.3390/v12010017

Herpesviruses usurp cellular stress responses to promote viral replication and avoid immune surveillance. The unfolded protein response (UPR) is a conserved stress response that is activated when the protein load in the ER exceeds folding capacity and misfolded proteins accumulate. The UPR aims to restore protein homeostasis through translational and transcriptional reprogramming; if homeostasis cannot be restored, the UPR switches from "helper" to "executioner", triggering apoptosis. It is thought that the burst of herpesvirus glycoprotein synthesis during lytic replication causes ER stress, and that these viruses may have evolved mechanisms to manage UPR signaling to create an optimal niche for replication. The past decade has seen considerable progress in understanding how herpesviruses reprogram the UPR. Here we provide an overview of the molecular events of UPR activation, signaling and transcriptional outputs, and highlight key evidence that herpesviruses hijack the UPR to aid infection.