Transmission of unfolded protein response—a regulator of disease progression, severity, and spread in virus infections

ABSTRACT The unfolded protein response (UPR) is a cell-autonomous stress response aimed at restoring homeostasis due to the accumulation of misfolded proteins in the endoplasmic reticulum (ER). Viruses often hijack the host cell machinery, leading to an accumulation of misfolded proteins in the ER....

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Main Author: Vibhu Prasad
Format: Article
Language:English
Published: American Society for Microbiology 2025-02-01
Series:mBio
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Online Access:https://journals.asm.org/doi/10.1128/mbio.03522-24
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author Vibhu Prasad
author_facet Vibhu Prasad
author_sort Vibhu Prasad
collection DOAJ
description ABSTRACT The unfolded protein response (UPR) is a cell-autonomous stress response aimed at restoring homeostasis due to the accumulation of misfolded proteins in the endoplasmic reticulum (ER). Viruses often hijack the host cell machinery, leading to an accumulation of misfolded proteins in the ER. The cell-autonomous UPR is the immediate response of an infected cell to this stress, aiming to restore normal function by halting protein translation, degrading misfolded proteins, and activating signaling pathways that increase the production of molecular chaperones. The cell-non-autonomous UPR involves the spreading of UPR signals from initially stressed cells to neighboring unstressed cells that lack the stressor. Though viruses are known modulators of cell-autonomous UPR, recent advancements have highlighted that cell-non-autonomous UPR plays a critical role in elucidating how local infections cause systemic effects, thereby contributing to disease symptoms and progression. Additionally, by utilizing cell-non-autonomous UPR, viruses have devised novel strategies to establish a pro-viral state, promoting virus spread. This review discusses examples that have broadened the understanding of the role of UPR in virus infections and disease progression by looking beyond cell-autonomous to non-autonomous processes and mechanistic details of the inducers, spreaders, and receivers of UPR signals.
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spelling doaj-art-7cf034f9b5f7409990baffb524e2ad562025-02-05T14:00:47ZengAmerican Society for MicrobiologymBio2150-75112025-02-0116210.1128/mbio.03522-24Transmission of unfolded protein response—a regulator of disease progression, severity, and spread in virus infectionsVibhu Prasad0Department of Infectious Diseases, Molecular Virology, Center for Integrative Infectious Disease Research, Medical Faculty Heidelberg, Heidelberg University, Heidelberg, GermanyABSTRACT The unfolded protein response (UPR) is a cell-autonomous stress response aimed at restoring homeostasis due to the accumulation of misfolded proteins in the endoplasmic reticulum (ER). Viruses often hijack the host cell machinery, leading to an accumulation of misfolded proteins in the ER. The cell-autonomous UPR is the immediate response of an infected cell to this stress, aiming to restore normal function by halting protein translation, degrading misfolded proteins, and activating signaling pathways that increase the production of molecular chaperones. The cell-non-autonomous UPR involves the spreading of UPR signals from initially stressed cells to neighboring unstressed cells that lack the stressor. Though viruses are known modulators of cell-autonomous UPR, recent advancements have highlighted that cell-non-autonomous UPR plays a critical role in elucidating how local infections cause systemic effects, thereby contributing to disease symptoms and progression. Additionally, by utilizing cell-non-autonomous UPR, viruses have devised novel strategies to establish a pro-viral state, promoting virus spread. This review discusses examples that have broadened the understanding of the role of UPR in virus infections and disease progression by looking beyond cell-autonomous to non-autonomous processes and mechanistic details of the inducers, spreaders, and receivers of UPR signals.https://journals.asm.org/doi/10.1128/mbio.03522-24unfolded protein response (UPR)virus infectionsdisease progressioncell-non-autonomous UPRpro-viral state
spellingShingle Vibhu Prasad
Transmission of unfolded protein response—a regulator of disease progression, severity, and spread in virus infections
mBio
unfolded protein response (UPR)
virus infections
disease progression
cell-non-autonomous UPR
pro-viral state
title Transmission of unfolded protein response—a regulator of disease progression, severity, and spread in virus infections
title_full Transmission of unfolded protein response—a regulator of disease progression, severity, and spread in virus infections
title_fullStr Transmission of unfolded protein response—a regulator of disease progression, severity, and spread in virus infections
title_full_unstemmed Transmission of unfolded protein response—a regulator of disease progression, severity, and spread in virus infections
title_short Transmission of unfolded protein response—a regulator of disease progression, severity, and spread in virus infections
title_sort transmission of unfolded protein response a regulator of disease progression severity and spread in virus infections
topic unfolded protein response (UPR)
virus infections
disease progression
cell-non-autonomous UPR
pro-viral state
url https://journals.asm.org/doi/10.1128/mbio.03522-24
work_keys_str_mv AT vibhuprasad transmissionofunfoldedproteinresponsearegulatorofdiseaseprogressionseverityandspreadinvirusinfections