Cellular resistance to an oncolytic virus is driven by chronic activation of innate immunity
Summary: The emergence of cellular resistances to oncolytic viruses is an underexplored process that could compromise the efficacy of cancer virotherapy. Here, we isolated and characterized B16 mouse melanoma cells that evolved resistance to an oncolytic vesicular stomatitis virus (VSV-D51). RNA-seq...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-01-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004222020223 |
| _version_ | 1797946170194001920 |
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| author | Alejandra Larrieux Rafael Sanjuán |
| author_facet | Alejandra Larrieux Rafael Sanjuán |
| author_sort | Alejandra Larrieux |
| collection | DOAJ |
| description | Summary: The emergence of cellular resistances to oncolytic viruses is an underexplored process that could compromise the efficacy of cancer virotherapy. Here, we isolated and characterized B16 mouse melanoma cells that evolved resistance to an oncolytic vesicular stomatitis virus (VSV-D51). RNA-seq revealed that resistance was associated to broad changes in gene expression, which typically involved chronic upregulation of interferon-stimulated genes. Innate immunity activation was maintained in the absence of the virus or other infection signals, and conferred cross-resistance to wild-type VSV and the unrelated Sindbis virus. Furthermore, we identified differentially expressed genes with no obvious role in antiviral immunity, such as Mnda, Psmb8 and Btn2a2, suggesting novel functions for these genes. Transcriptomic changes associated to VSV resistance were similar among B16 clones and in some clones derived from the mouse colon carcinoma cell line CT26, suggesting that oncolytic virus resistance involves certain conserved mechanisms and is therefore a potentially predictable process. |
| first_indexed | 2024-04-10T21:06:38Z |
| format | Article |
| id | doaj.art-8765603c9a8646f187c79bdb371b8935 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-10T21:06:38Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-8765603c9a8646f187c79bdb371b89352023-01-22T04:40:43ZengElsevieriScience2589-00422023-01-01261105749Cellular resistance to an oncolytic virus is driven by chronic activation of innate immunityAlejandra Larrieux0Rafael Sanjuán1Institute for Integrative Systems Biology (I2SysBio), Universitat de València-CSIC, Paterna, València 46980, SpainInstitute for Integrative Systems Biology (I2SysBio), Universitat de València-CSIC, Paterna, València 46980, Spain; Corresponding authorSummary: The emergence of cellular resistances to oncolytic viruses is an underexplored process that could compromise the efficacy of cancer virotherapy. Here, we isolated and characterized B16 mouse melanoma cells that evolved resistance to an oncolytic vesicular stomatitis virus (VSV-D51). RNA-seq revealed that resistance was associated to broad changes in gene expression, which typically involved chronic upregulation of interferon-stimulated genes. Innate immunity activation was maintained in the absence of the virus or other infection signals, and conferred cross-resistance to wild-type VSV and the unrelated Sindbis virus. Furthermore, we identified differentially expressed genes with no obvious role in antiviral immunity, such as Mnda, Psmb8 and Btn2a2, suggesting novel functions for these genes. Transcriptomic changes associated to VSV resistance were similar among B16 clones and in some clones derived from the mouse colon carcinoma cell line CT26, suggesting that oncolytic virus resistance involves certain conserved mechanisms and is therefore a potentially predictable process.http://www.sciencedirect.com/science/article/pii/S2589004222020223Molecular physiologyImmunologyVirology |
| spellingShingle | Alejandra Larrieux Rafael Sanjuán Cellular resistance to an oncolytic virus is driven by chronic activation of innate immunity iScience Molecular physiology Immunology Virology |
| title | Cellular resistance to an oncolytic virus is driven by chronic activation of innate immunity |
| title_full | Cellular resistance to an oncolytic virus is driven by chronic activation of innate immunity |
| title_fullStr | Cellular resistance to an oncolytic virus is driven by chronic activation of innate immunity |
| title_full_unstemmed | Cellular resistance to an oncolytic virus is driven by chronic activation of innate immunity |
| title_short | Cellular resistance to an oncolytic virus is driven by chronic activation of innate immunity |
| title_sort | cellular resistance to an oncolytic virus is driven by chronic activation of innate immunity |
| topic | Molecular physiology Immunology Virology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004222020223 |
| work_keys_str_mv | AT alejandralarrieux cellularresistancetoanoncolyticvirusisdrivenbychronicactivationofinnateimmunity AT rafaelsanjuan cellularresistancetoanoncolyticvirusisdrivenbychronicactivationofinnateimmunity |