Wuhan strain of SARS-CoV-2 triggers activation of immune evasion machinery similar to the one operated by cancer cells
In the last 2 years, there has been an increasing concern that SARS-CoV-2 infection may represent a marker of undiagnosed cancers. A potential connection between COVID-19/long COVID and malignant transformation/cancer progression was reported in a number of studies. It is, however, unclear if the vi...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2025-06-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1599352/full |
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| author | Maryam Abooali Inna M. Yasinska Gauri Thapa Xi Lei Kelly A. S. da Costa Stephanie Schlichtner Stephanie Schlichtner Stephanie Schlichtner Steffen M. Berger Elizaveta Fasler-Kan Nigel J. Temperton Romina Vuono Vadim V. Sumbayev |
| author_facet | Maryam Abooali Inna M. Yasinska Gauri Thapa Xi Lei Kelly A. S. da Costa Stephanie Schlichtner Stephanie Schlichtner Stephanie Schlichtner Steffen M. Berger Elizaveta Fasler-Kan Nigel J. Temperton Romina Vuono Vadim V. Sumbayev |
| author_sort | Maryam Abooali |
| collection | DOAJ |
| description | In the last 2 years, there has been an increasing concern that SARS-CoV-2 infection may represent a marker of undiagnosed cancers. A potential connection between COVID-19/long COVID and malignant transformation/cancer progression was reported in a number of studies. It is, however, unclear if the virus itself can cause malignant transformation or if it has a potential to support malignant processes in human body. We analyzed nasopharyngeal swabs collected from individuals infected with Wuhan strain of SARS-CoV-2 and conducted in vitro studies using BEAS-2B human bronchial epithelial cells. Here we report that Wuhan strain of SARS-CoV-2 and its spike protein induce activation of hypoxia-inducible factor 1 (HIF-1) transcription complex in infected cells. This effect is achieved through conversion of cellular 2-oxoglutarate into 2-hydroxy-glutarate, which most likely blocks the activity of HIF-1α prolyl hydroxylation. As such, it leads to activation of HIF-1, which triggers production of transforming growth factor–β type 1 (TGF-β). TGF-β induces expression of immune checkpoint proteins, such as galectin-9, programmed death-ligand 1, and indoleamine-2,3-dioxygenase, an enzyme, which is involved in production of immunosuppressive amino acid called L-kynurenine. These immune checkpoint pathways were capable of suppressing both helper and cytotoxic activities of T lymphocytes and, as such, could potentially support malignant processes in infected tissues. |
| format | Article |
| id | doaj-art-aaed9dd9967a413dbe108126cf4263e9 |
| institution | DOAJ |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-aaed9dd9967a413dbe108126cf4263e92025-08-20T03:22:03ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-06-011610.3389/fimmu.2025.15993521599352Wuhan strain of SARS-CoV-2 triggers activation of immune evasion machinery similar to the one operated by cancer cellsMaryam Abooali0Inna M. Yasinska1Gauri Thapa2Xi Lei3Kelly A. S. da Costa4Stephanie Schlichtner5Stephanie Schlichtner6Stephanie Schlichtner7Steffen M. Berger8Elizaveta Fasler-Kan9Nigel J. Temperton10Romina Vuono11Vadim V. Sumbayev12Medway School of Pharmacy, Universities of Kent and Greenwich, Chatham, United KingdomMedway School of Pharmacy, Universities of Kent and Greenwich, Chatham, United KingdomMedway School of Pharmacy, Universities of Kent and Greenwich, Chatham, United KingdomMedway School of Pharmacy, Universities of Kent and Greenwich, Chatham, United KingdomMedway School of Pharmacy, Universities of Kent and Greenwich, Chatham, United KingdomDKFZ-Hector Cancer Institute at the University Medical Center Mannheim, Mannheim, GermanyDivision of Personalized Medical Oncology (A420), German Cancer Research Center (DKFZ), Heidelberg, GermanyDepartment of Personalized Oncology, University Hospital Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, GermanyDepartment of Pediatric Surgery, Children’s Hospital, Inselspital Bern, University of Bern and Department of Biomedical Research, University of Bern, Bern, SwitzerlandDepartment of Pediatric Surgery, Children’s Hospital, Inselspital Bern, University of Bern and Department of Biomedical Research, University of Bern, Bern, SwitzerlandMedway School of Pharmacy, Universities of Kent and Greenwich, Chatham, United KingdomMedway School of Pharmacy, Universities of Kent and Greenwich, Chatham, United KingdomMedway School of Pharmacy, Universities of Kent and Greenwich, Chatham, United KingdomIn the last 2 years, there has been an increasing concern that SARS-CoV-2 infection may represent a marker of undiagnosed cancers. A potential connection between COVID-19/long COVID and malignant transformation/cancer progression was reported in a number of studies. It is, however, unclear if the virus itself can cause malignant transformation or if it has a potential to support malignant processes in human body. We analyzed nasopharyngeal swabs collected from individuals infected with Wuhan strain of SARS-CoV-2 and conducted in vitro studies using BEAS-2B human bronchial epithelial cells. Here we report that Wuhan strain of SARS-CoV-2 and its spike protein induce activation of hypoxia-inducible factor 1 (HIF-1) transcription complex in infected cells. This effect is achieved through conversion of cellular 2-oxoglutarate into 2-hydroxy-glutarate, which most likely blocks the activity of HIF-1α prolyl hydroxylation. As such, it leads to activation of HIF-1, which triggers production of transforming growth factor–β type 1 (TGF-β). TGF-β induces expression of immune checkpoint proteins, such as galectin-9, programmed death-ligand 1, and indoleamine-2,3-dioxygenase, an enzyme, which is involved in production of immunosuppressive amino acid called L-kynurenine. These immune checkpoint pathways were capable of suppressing both helper and cytotoxic activities of T lymphocytes and, as such, could potentially support malignant processes in infected tissues.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1599352/fullSARS-CoV-2COVID-19cancerimmune checkpointsimmune evasion |
| spellingShingle | Maryam Abooali Inna M. Yasinska Gauri Thapa Xi Lei Kelly A. S. da Costa Stephanie Schlichtner Stephanie Schlichtner Stephanie Schlichtner Steffen M. Berger Elizaveta Fasler-Kan Nigel J. Temperton Romina Vuono Vadim V. Sumbayev Wuhan strain of SARS-CoV-2 triggers activation of immune evasion machinery similar to the one operated by cancer cells Frontiers in Immunology SARS-CoV-2 COVID-19 cancer immune checkpoints immune evasion |
| title | Wuhan strain of SARS-CoV-2 triggers activation of immune evasion machinery similar to the one operated by cancer cells |
| title_full | Wuhan strain of SARS-CoV-2 triggers activation of immune evasion machinery similar to the one operated by cancer cells |
| title_fullStr | Wuhan strain of SARS-CoV-2 triggers activation of immune evasion machinery similar to the one operated by cancer cells |
| title_full_unstemmed | Wuhan strain of SARS-CoV-2 triggers activation of immune evasion machinery similar to the one operated by cancer cells |
| title_short | Wuhan strain of SARS-CoV-2 triggers activation of immune evasion machinery similar to the one operated by cancer cells |
| title_sort | wuhan strain of sars cov 2 triggers activation of immune evasion machinery similar to the one operated by cancer cells |
| topic | SARS-CoV-2 COVID-19 cancer immune checkpoints immune evasion |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1599352/full |
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