Journal Article

DKFZ-2025-01413

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Wuhan strain of SARS-CoV-2 triggers activation of immune evasion machinery similar to the one operated by cancer cells.

Abooali, M. ; Yasinska, I. M. ; Thapa, G. ; Lei, X. ; da Costa, K. A. S. ; Schlichtner, S.DKFZ* ; Berger, S. M. ; Fasler-Kan, E. ; Temperton, N. J. ; Vuono, R. ; Sumbayev, V. V.

2025
Frontiers Media Lausanne

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Please use a persistent id in citations: doi:10.3389/fimmu.2025.1599352

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.

Keyword(s): Humans (MeSH) ; SARS-CoV-2: immunology (MeSH) ; COVID-19: immunology (MeSH) ; COVID-19: virology (MeSH) ; Immune Evasion: immunology (MeSH) ; Hypoxia-Inducible Factor 1, alpha Subunit: metabolism (MeSH) ; Spike Glycoprotein, Coronavirus: immunology (MeSH) ; Spike Glycoprotein, Coronavirus: metabolism (MeSH) ; Indoleamine-Pyrrole 2,3,-Dioxygenase: metabolism (MeSH) ; Epithelial Cells: immunology (MeSH) ; Epithelial Cells: virology (MeSH) ; Cell Line (MeSH) ; B7-H1 Antigen: metabolism (MeSH) ; Neoplasms: immunology (MeSH) ; Ketoglutaric Acids: metabolism (MeSH) ; COVID-19 ; SARS-CoV-2 ; cancer ; immune checkpoints ; immune evasion ; Hypoxia-Inducible Factor 1, alpha Subunit ; HIF1A protein, human ; Spike Glycoprotein, Coronavirus ; Indoleamine-Pyrrole 2,3,-Dioxygenase ; spike protein, SARS-CoV-2 ; B7-H1 Antigen ; Ketoglutaric Acids ; CD274 protein, human

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Contributing Institute(s):

1. Personalisierte Medizinische Onkologie (A420)

Research Program(s):

1. 311 - Zellbiologie und Tumorbiologie (POF4-311) (POF4-311)

Appears in the scientific report 2025

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Database coverage:
; ; ; Article Processing Charges ; Clarivate Analytics Master Journal List ; DOAJ Seal ; Essential Science Indicators ; Fees ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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