TY  - JOUR
AU  - Abooali, Maryam
AU  - Yasinska, Inna M
AU  - Thapa, Gauri
AU  - Lei, Xi
AU  - da Costa, Kelly A S
AU  - Schlichtner, Stephanie
AU  - Berger, Steffen M
AU  - Fasler-Kan, Elizaveta
AU  - Temperton, Nigel J
AU  - Vuono, Romina
AU  - Sumbayev, Vadim V
TI  - Wuhan strain of SARS-CoV-2 triggers activation of immune evasion machinery similar to the one operated by cancer cells.
JO  - Frontiers in immunology
VL  - 16
SN  - 1664-3224
CY  - Lausanne
PB  - Frontiers Media
M1  - DKFZ-2025-01413
SP  - 1599352
PY  - 2025
AB  - 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.
KW  - Humans
KW  - SARS-CoV-2: immunology
KW  - COVID-19: immunology
KW  - COVID-19: virology
KW  - Immune Evasion: immunology
KW  - Hypoxia-Inducible Factor 1, alpha Subunit: metabolism
KW  - Spike Glycoprotein, Coronavirus: immunology
KW  - Spike Glycoprotein, Coronavirus: metabolism
KW  - Indoleamine-Pyrrole 2,3,-Dioxygenase: metabolism
KW  - Epithelial Cells: immunology
KW  - Epithelial Cells: virology
KW  - Cell Line
KW  - B7-H1 Antigen: metabolism
KW  - Neoplasms: immunology
KW  - Ketoglutaric Acids: metabolism
KW  - COVID-19 (Other)
KW  - SARS-CoV-2 (Other)
KW  - cancer (Other)
KW  - immune checkpoints (Other)
KW  - immune evasion (Other)
KW  - Hypoxia-Inducible Factor 1, alpha Subunit (NLM Chemicals)
KW  - HIF1A protein, human (NLM Chemicals)
KW  - Spike Glycoprotein, Coronavirus (NLM Chemicals)
KW  - Indoleamine-Pyrrole 2,3,-Dioxygenase (NLM Chemicals)
KW  - spike protein, SARS-CoV-2 (NLM Chemicals)
KW  - B7-H1 Antigen (NLM Chemicals)
KW  - Ketoglutaric Acids (NLM Chemicals)
KW  - CD274 protein, human (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:40607414
C2  - pmc:PMC12213721
DO  - DOI:10.3389/fimmu.2025.1599352
UR  - https://inrepo02.dkfz.de/record/302873
ER  -