%0 Journal Article
%A Abooali, Maryam
%A Yasinska, Inna M
%A Thapa, Gauri
%A Lei, Xi
%A da Costa, Kelly A S
%A Schlichtner, Stephanie
%A Berger, Steffen M
%A Fasler-Kan, Elizaveta
%A Temperton, Nigel J
%A Vuono, Romina
%A Sumbayev, Vadim V
%T Wuhan strain of SARS-CoV-2 triggers activation of immune evasion machinery similar to the one operated by cancer cells.
%J Frontiers in immunology
%V 16
%@ 1664-3224
%C Lausanne
%I Frontiers Media
%M DKFZ-2025-01413
%P 1599352
%D 2025
%X 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.
%K Humans
%K SARS-CoV-2: immunology
%K COVID-19: immunology
%K COVID-19: virology
%K Immune Evasion: immunology
%K Hypoxia-Inducible Factor 1, alpha Subunit: metabolism
%K Spike Glycoprotein, Coronavirus: immunology
%K Spike Glycoprotein, Coronavirus: metabolism
%K Indoleamine-Pyrrole 2,3,-Dioxygenase: metabolism
%K Epithelial Cells: immunology
%K Epithelial Cells: virology
%K Cell Line
%K B7-H1 Antigen: metabolism
%K Neoplasms: immunology
%K Ketoglutaric Acids: metabolism
%K COVID-19 (Other)
%K SARS-CoV-2 (Other)
%K cancer (Other)
%K immune checkpoints (Other)
%K immune evasion (Other)
%K Hypoxia-Inducible Factor 1, alpha Subunit (NLM Chemicals)
%K HIF1A protein, human (NLM Chemicals)
%K Spike Glycoprotein, Coronavirus (NLM Chemicals)
%K Indoleamine-Pyrrole 2,3,-Dioxygenase (NLM Chemicals)
%K spike protein, SARS-CoV-2 (NLM Chemicals)
%K B7-H1 Antigen (NLM Chemicals)
%K Ketoglutaric Acids (NLM Chemicals)
%K CD274 protein, human (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:40607414
%2 pmc:PMC12213721
%R 10.3389/fimmu.2025.1599352
%U https://inrepo02.dkfz.de/record/302873