Human Betacoronavirus OC43 Interferes with the Integrated Stress Response Pathway in Infected Cells
Viruses evolve many strategies to ensure the efficient synthesis of their proteins. One such strategy is the inhibition of the integrated stress response—the mechanism through which infected cells arrest translation through the phosphorylation of the alpha subunit of the eukaryotic translation initi...
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-01-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/16/2/212 |
| _version_ | 1797296843120443392 |
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| author | Stacia M. Dolliver Caleb Galbraith Denys A. Khaperskyy |
| author_facet | Stacia M. Dolliver Caleb Galbraith Denys A. Khaperskyy |
| author_sort | Stacia M. Dolliver |
| collection | DOAJ |
| description | Viruses evolve many strategies to ensure the efficient synthesis of their proteins. One such strategy is the inhibition of the integrated stress response—the mechanism through which infected cells arrest translation through the phosphorylation of the alpha subunit of the eukaryotic translation initiation factor 2 (eIF2α). We have recently shown that the human common cold betacoronavirus OC43 actively inhibits eIF2α phosphorylation in response to sodium arsenite, a potent inducer of oxidative stress. In this work, we examined the modulation of integrated stress responses by OC43 and demonstrated that the negative feedback regulator of eIF2α phosphorylation GADD34 is strongly induced in infected cells. However, the upregulation of GADD34 expression induced by OC43 was independent from the activation of the integrated stress response and was not required for the inhibition of eIF2α phosphorylation in virus-infected cells. Our work reveals a complex interplay between the common cold coronavirus and the integrated stress response, in which efficient viral protein synthesis is ensured by the inhibition of eIF2α phosphorylation but the GADD34 negative feedback loop is disrupted. |
| first_indexed | 2024-03-07T22:11:38Z |
| format | Article |
| id | doaj.art-fc69a40df7c2496c9f1124e0d55358f7 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-07T22:11:38Z |
| publishDate | 2024-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-fc69a40df7c2496c9f1124e0d55358f72024-02-23T15:37:30ZengMDPI AGViruses1999-49152024-01-0116221210.3390/v16020212Human Betacoronavirus OC43 Interferes with the Integrated Stress Response Pathway in Infected CellsStacia M. Dolliver0Caleb Galbraith1Denys A. Khaperskyy2Department of Microbiology and Immunology, Faculty of Medicine, Dalhousie University, Halifax, NS B3H 4R2, CanadaDepartment of Microbiology and Immunology, Faculty of Medicine, Dalhousie University, Halifax, NS B3H 4R2, CanadaDepartment of Microbiology and Immunology, Faculty of Medicine, Dalhousie University, Halifax, NS B3H 4R2, CanadaViruses evolve many strategies to ensure the efficient synthesis of their proteins. One such strategy is the inhibition of the integrated stress response—the mechanism through which infected cells arrest translation through the phosphorylation of the alpha subunit of the eukaryotic translation initiation factor 2 (eIF2α). We have recently shown that the human common cold betacoronavirus OC43 actively inhibits eIF2α phosphorylation in response to sodium arsenite, a potent inducer of oxidative stress. In this work, we examined the modulation of integrated stress responses by OC43 and demonstrated that the negative feedback regulator of eIF2α phosphorylation GADD34 is strongly induced in infected cells. However, the upregulation of GADD34 expression induced by OC43 was independent from the activation of the integrated stress response and was not required for the inhibition of eIF2α phosphorylation in virus-infected cells. Our work reveals a complex interplay between the common cold coronavirus and the integrated stress response, in which efficient viral protein synthesis is ensured by the inhibition of eIF2α phosphorylation but the GADD34 negative feedback loop is disrupted.https://www.mdpi.com/1999-4915/16/2/212betacoronavirus OC43integrated stress responsePERKPKRGADD34ATF4 |
| spellingShingle | Stacia M. Dolliver Caleb Galbraith Denys A. Khaperskyy Human Betacoronavirus OC43 Interferes with the Integrated Stress Response Pathway in Infected Cells Viruses betacoronavirus OC43 integrated stress response PERK PKR GADD34 ATF4 |
| title | Human Betacoronavirus OC43 Interferes with the Integrated Stress Response Pathway in Infected Cells |
| title_full | Human Betacoronavirus OC43 Interferes with the Integrated Stress Response Pathway in Infected Cells |
| title_fullStr | Human Betacoronavirus OC43 Interferes with the Integrated Stress Response Pathway in Infected Cells |
| title_full_unstemmed | Human Betacoronavirus OC43 Interferes with the Integrated Stress Response Pathway in Infected Cells |
| title_short | Human Betacoronavirus OC43 Interferes with the Integrated Stress Response Pathway in Infected Cells |
| title_sort | human betacoronavirus oc43 interferes with the integrated stress response pathway in infected cells |
| topic | betacoronavirus OC43 integrated stress response PERK PKR GADD34 ATF4 |
| url | https://www.mdpi.com/1999-4915/16/2/212 |
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