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@ARTICLE{Abooali:302873,
      author       = {M. Abooali and I. M. Yasinska and G. Thapa and X. Lei and
                      K. A. S. da Costa and S. Schlichtner$^*$ and S. M. Berger
                      and E. Fasler-Kan and N. J. Temperton and R. Vuono and V. V.
                      Sumbayev},
      title        = {{W}uhan strain of {SARS}-{C}o{V}-2 triggers activation of
                      immune evasion machinery similar to the one operated by
                      cancer cells.},
      journal      = {Frontiers in immunology},
      volume       = {16},
      issn         = {1664-3224},
      address      = {Lausanne},
      publisher    = {Frontiers Media},
      reportid     = {DKFZ-2025-01413},
      pages        = {1599352},
      year         = {2025},
      abstract     = {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.},
      keywords     = {Humans / SARS-CoV-2: immunology / COVID-19: immunology /
                      COVID-19: virology / Immune Evasion: immunology /
                      Hypoxia-Inducible Factor 1, alpha Subunit: metabolism /
                      Spike Glycoprotein, Coronavirus: immunology / Spike
                      Glycoprotein, Coronavirus: metabolism / Indoleamine-Pyrrole
                      2,3,-Dioxygenase: metabolism / Epithelial Cells: immunology
                      / Epithelial Cells: virology / Cell Line / B7-H1 Antigen:
                      metabolism / Neoplasms: immunology / Ketoglutaric Acids:
                      metabolism / COVID-19 (Other) / SARS-CoV-2 (Other) / cancer
                      (Other) / immune checkpoints (Other) / immune evasion
                      (Other) / Hypoxia-Inducible Factor 1, alpha Subunit (NLM
                      Chemicals) / HIF1A protein, human (NLM Chemicals) / Spike
                      Glycoprotein, Coronavirus (NLM Chemicals) /
                      Indoleamine-Pyrrole 2,3,-Dioxygenase (NLM Chemicals) / spike
                      protein, SARS-CoV-2 (NLM Chemicals) / B7-H1 Antigen (NLM
                      Chemicals) / Ketoglutaric Acids (NLM Chemicals) / CD274
                      protein, human (NLM Chemicals)},
      cin          = {A420},
      ddc          = {610},
      cid          = {I:(DE-He78)A420-20160331},
      pnm          = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
      pid          = {G:(DE-HGF)POF4-311},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40607414},
      pmc          = {pmc:PMC12213721},
      doi          = {10.3389/fimmu.2025.1599352},
      url          = {https://inrepo02.dkfz.de/record/302873},
}