Fatty acid desaturases link cell metabolism pathways to promote proliferation of Epstein-Barr virus-infected B cells.
Epstein-Barr virus (EBV) is a gamma herpesvirus that infects up to 95% of the human population by adulthood, typically remaining latent in the host memory B cell pool. In immunocompromised individuals, EBV can drive the transformation and rapid proliferation of infected B cells, ultimately resulting...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2025-05-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1012685 |
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| author | Emmanuela N Bonglack Kaeden K Hill Ashley P Barry Alexandria Bartlett Pol Castellano-Escuder Matthew D Hirschey Micah A Luftig |
| author_facet | Emmanuela N Bonglack Kaeden K Hill Ashley P Barry Alexandria Bartlett Pol Castellano-Escuder Matthew D Hirschey Micah A Luftig |
| author_sort | Emmanuela N Bonglack |
| collection | DOAJ |
| description | Epstein-Barr virus (EBV) is a gamma herpesvirus that infects up to 95% of the human population by adulthood, typically remaining latent in the host memory B cell pool. In immunocompromised individuals, EBV can drive the transformation and rapid proliferation of infected B cells, ultimately resulting in neoplasia. The same transformation process can be induced in vitro, with EBV-infected peripheral blood B cells forming immortalized lymphoblastoid cell lines (LCLs) within weeks. In this study, we found that the fatty acid desaturases stearoyl-CoA desaturase 1 (SCD1) and fatty acid desaturase 2 (FADS2) are upregulated by EBV and crucial for EBV-induced B cell proliferation. We show that pharmacological and genetic inhibition of both SCD1 and FADS2 results in a significantly greater reduction in proliferation and cell cycle arrest, compared to perturbing either enzyme individually. Additionally, we found that inhibiting either SCD1 or FADS2 alone hypersensitizes LCLs to palmitate-induced apoptosis. Further free fatty acid profiling and metabolic analysis of dual SCD1/FADS2-inhibited LCLs revealed an increase in free unsaturated fatty acids, a reduction of oxidative phosphorylation, and a reduction of glycolysis, thereby linking the activity of SCD1 and FADS2 to overall growth-promoting metabolism. Lastly, we show that SCD1 and FADS2 are important in the growth of clinically derived EBV+ immunoblastic lymphoma cells. Collectively, these data demonstrate a previously uncharacterized role of lipid desaturation in EBV+ transformed B cell proliferation, revealing a metabolic pathway that can be targeted in future anti-lymphoma therapies. |
| format | Article |
| id | doaj-art-bd2531235bd64bc6ba5eeb2c1ef0c2ba |
| institution | Kabale University |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-bd2531235bd64bc6ba5eeb2c1ef0c2ba2025-08-20T03:25:45ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742025-05-01215e101268510.1371/journal.ppat.1012685Fatty acid desaturases link cell metabolism pathways to promote proliferation of Epstein-Barr virus-infected B cells.Emmanuela N BonglackKaeden K HillAshley P BarryAlexandria BartlettPol Castellano-EscuderMatthew D HirscheyMicah A LuftigEpstein-Barr virus (EBV) is a gamma herpesvirus that infects up to 95% of the human population by adulthood, typically remaining latent in the host memory B cell pool. In immunocompromised individuals, EBV can drive the transformation and rapid proliferation of infected B cells, ultimately resulting in neoplasia. The same transformation process can be induced in vitro, with EBV-infected peripheral blood B cells forming immortalized lymphoblastoid cell lines (LCLs) within weeks. In this study, we found that the fatty acid desaturases stearoyl-CoA desaturase 1 (SCD1) and fatty acid desaturase 2 (FADS2) are upregulated by EBV and crucial for EBV-induced B cell proliferation. We show that pharmacological and genetic inhibition of both SCD1 and FADS2 results in a significantly greater reduction in proliferation and cell cycle arrest, compared to perturbing either enzyme individually. Additionally, we found that inhibiting either SCD1 or FADS2 alone hypersensitizes LCLs to palmitate-induced apoptosis. Further free fatty acid profiling and metabolic analysis of dual SCD1/FADS2-inhibited LCLs revealed an increase in free unsaturated fatty acids, a reduction of oxidative phosphorylation, and a reduction of glycolysis, thereby linking the activity of SCD1 and FADS2 to overall growth-promoting metabolism. Lastly, we show that SCD1 and FADS2 are important in the growth of clinically derived EBV+ immunoblastic lymphoma cells. Collectively, these data demonstrate a previously uncharacterized role of lipid desaturation in EBV+ transformed B cell proliferation, revealing a metabolic pathway that can be targeted in future anti-lymphoma therapies.https://doi.org/10.1371/journal.ppat.1012685 |
| spellingShingle | Emmanuela N Bonglack Kaeden K Hill Ashley P Barry Alexandria Bartlett Pol Castellano-Escuder Matthew D Hirschey Micah A Luftig Fatty acid desaturases link cell metabolism pathways to promote proliferation of Epstein-Barr virus-infected B cells. PLoS Pathogens |
| title | Fatty acid desaturases link cell metabolism pathways to promote proliferation of Epstein-Barr virus-infected B cells. |
| title_full | Fatty acid desaturases link cell metabolism pathways to promote proliferation of Epstein-Barr virus-infected B cells. |
| title_fullStr | Fatty acid desaturases link cell metabolism pathways to promote proliferation of Epstein-Barr virus-infected B cells. |
| title_full_unstemmed | Fatty acid desaturases link cell metabolism pathways to promote proliferation of Epstein-Barr virus-infected B cells. |
| title_short | Fatty acid desaturases link cell metabolism pathways to promote proliferation of Epstein-Barr virus-infected B cells. |
| title_sort | fatty acid desaturases link cell metabolism pathways to promote proliferation of epstein barr virus infected b cells |
| url | https://doi.org/10.1371/journal.ppat.1012685 |
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