Abstract
Viral infection induces endoplasmic reticulum (ER) stress and interferon responses. While viral double-stranded RNA intermediates trigger interferon responses, viral polypeptides synthesized during infection stimulate ER stress. Among the interferon-regulated gene products, the double-stranded RNA-dependent protein kinase (PKR) plays a key role in limiting viral replication. Thus, to establish productive infection, viruses have evolved mechanisms to overcome the deleterious effects of PKR. It has become clear that ER stress causes translational attenuation and transcriptional upregulation of genes encoding proteins that facilitate folding or degradation of proteins. Notably, prolonged ER stress triggers apoptosis. Therefore, viruses are confronted with the consequences of ER stress. Emerging evidence suggests that viruses not only interfere with the interferon system involving PKR but also manipulate the programs emanating from the ER in a complex way, which may facilitate viral replication or pathogenesis. This review highlights recent progress in these areas.
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Abbreviations
- ATF4:
-
activating transcription factor 4
- ATF6:
-
activating transcription factor 6
- BiP:
-
the ER chaperone immunoglobulin heavy-chain-binding protein
- CHOP:
-
C/EBP homologous protein
- dsDNA:
-
double-stranded DNA
- ER:
-
endoplasmic reticulum
- GADD34:
-
growth arrest and DNA damage-inducible protein 34
- IRE1:
-
ER transmembrane protein kinase/endoribonuclease
- PACT:
-
PKR-activating protein
- PERK:
-
PKR-like ER kinase
- PKR:
-
double-stranded RNA-dependent protein kinase
- ssRNA:
-
single-stranded RNA
- UPR:
-
the unfolded protein response
- XBP1:
-
X-box-binding protein
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Acknowledgements
The work in this laboratory was supported by grant AI 46665 (BH) from the National Institute of Allergy and Infectious Diseases. I thank Dustin Verpooten for critical reading of the manuscript.
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He, B. Viruses, endoplasmic reticulum stress, and interferon responses. Cell Death Differ 13, 393–403 (2006). https://doi.org/10.1038/sj.cdd.4401833
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DOI: https://doi.org/10.1038/sj.cdd.4401833


