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000302873 041__ $$aEnglish
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000302873 1001_ $$aAbooali, Maryam$$b0
000302873 245__ $$aWuhan strain of SARS-CoV-2 triggers activation of immune evasion machinery similar to the one operated by cancer cells.
000302873 260__ $$aLausanne$$bFrontiers Media$$c2025
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000302873 520__ $$aIn 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.
000302873 536__ $$0G:(DE-HGF)POF4-311$$a311 - Zellbiologie und Tumorbiologie (POF4-311)$$cPOF4-311$$fPOF IV$$x0
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000302873 650_7 $$2Other$$aCOVID-19
000302873 650_7 $$2Other$$aSARS-CoV-2
000302873 650_7 $$2Other$$acancer
000302873 650_7 $$2Other$$aimmune checkpoints
000302873 650_7 $$2Other$$aimmune evasion
000302873 650_7 $$2NLM Chemicals$$aHypoxia-Inducible Factor 1, alpha Subunit
000302873 650_7 $$2NLM Chemicals$$aHIF1A protein, human
000302873 650_7 $$2NLM Chemicals$$aSpike Glycoprotein, Coronavirus
000302873 650_7 $$2NLM Chemicals$$aIndoleamine-Pyrrole 2,3,-Dioxygenase
000302873 650_7 $$2NLM Chemicals$$aspike protein, SARS-CoV-2
000302873 650_7 $$2NLM Chemicals$$aB7-H1 Antigen
000302873 650_7 $$2NLM Chemicals$$aKetoglutaric Acids
000302873 650_7 $$2NLM Chemicals$$aCD274 protein, human
000302873 650_2 $$2MeSH$$aHumans
000302873 650_2 $$2MeSH$$aSARS-CoV-2: immunology
000302873 650_2 $$2MeSH$$aCOVID-19: immunology
000302873 650_2 $$2MeSH$$aCOVID-19: virology
000302873 650_2 $$2MeSH$$aImmune Evasion: immunology
000302873 650_2 $$2MeSH$$aHypoxia-Inducible Factor 1, alpha Subunit: metabolism
000302873 650_2 $$2MeSH$$aSpike Glycoprotein, Coronavirus: immunology
000302873 650_2 $$2MeSH$$aSpike Glycoprotein, Coronavirus: metabolism
000302873 650_2 $$2MeSH$$aIndoleamine-Pyrrole 2,3,-Dioxygenase: metabolism
000302873 650_2 $$2MeSH$$aEpithelial Cells: immunology
000302873 650_2 $$2MeSH$$aEpithelial Cells: virology
000302873 650_2 $$2MeSH$$aCell Line
000302873 650_2 $$2MeSH$$aB7-H1 Antigen: metabolism
000302873 650_2 $$2MeSH$$aNeoplasms: immunology
000302873 650_2 $$2MeSH$$aKetoglutaric Acids: metabolism
000302873 7001_ $$aYasinska, Inna M$$b1
000302873 7001_ $$aThapa, Gauri$$b2
000302873 7001_ $$aLei, Xi$$b3
000302873 7001_ $$ada Costa, Kelly A S$$b4
000302873 7001_ $$0P:(DE-He78)0b6e32bf4b6d335c6b11d5edaef8bfd3$$aSchlichtner, Stephanie$$b5$$udkfz
000302873 7001_ $$aBerger, Steffen M$$b6
000302873 7001_ $$aFasler-Kan, Elizaveta$$b7
000302873 7001_ $$aTemperton, Nigel J$$b8
000302873 7001_ $$aVuono, Romina$$b9
000302873 7001_ $$aSumbayev, Vadim V$$b10
000302873 773__ $$0PERI:(DE-600)2606827-8$$a10.3389/fimmu.2025.1599352$$gVol. 16, p. 1599352$$p1599352$$tFrontiers in immunology$$v16$$x1664-3224$$y2025
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