Modulation of endoplasmic reticulum stress response pathways by respiratory viruses

Abstract

Acute respiratory infections (ARIs) are amongst the leading causes of death and disability, and the greatest burden of disease impacts children, pregnant women, and the elderly. Respiratory viruses account for the majority of ARIs. The unfolded protein response (UPR) is a host homeostatic defence mechanism primarily activated in response to aberrant endoplasmic reticulum (ER) resident protein accumulation in cell stresses including viral infection. The UPR has been implicated in the pathogenesis of several respiratory diseases, as the respiratory system is particularly vulnerable to chronic and acute activation of the ER stress response pathway. Many respiratory viruses therefore employ strategies to modulate the UPR during infection, with varying effects on the host and the pathogens. Here, we review the specific means by which respiratory viruses affect the host UPR, particularly in association with the high production of viral glycoproteins, and the impact of UPR activation and subversion on viral replication and disease pathogenesis. We further review the activation of UPR in common co-morbidities of ARIs and discuss the therapeutic potential of modulating the UPR in virally induced respiratory diseases.

Keywords:

• Respiratory virus infection
• virus-host biology
• unfolded protein response
• glycoproteins
• viral replication
• influenza virus
• respiratory syncytial virus
• coronavirus

Authors’ contributions

All authors wrote and reviewed the manuscript. KLM designed the figures.

Disclosure statement

The authors report there are no competing interests to declare.

Data availability statement

Data sharing is not applicable to this article as no new data were created or analyzed in this study.

Additional information

Funding

This work was supported by the NHMRC Ideas Grant scheme under grant [number APP1186699].