Publication Database

Epithelial response to IFN-γ promotes SARS-CoV-2 infection (2021)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Heuberger, Julian

Trimpert, Jakob (WE 5)

Vladimirova, Daria (WE 5)

Goosmann, Christian

Lin, Manqiang

Schmuck, Rosa

Mollenkopf, Hans-Joachim

Brinkmann, Volker

Tacke, Frank

Osterrieder, Nikolaus (WE 5)

Sigal, Michael

Quelle

EMBO molecular medicine

Bandzählung: 13

Heftzählung: 4

Seiten: Artikel e13191

ISSN: 1757-4676

Sprache

Englisch

Verweise

URL (Volltext): https://www.embopress.org/doi/full/10.15252/emmm.202013191

DOI: 10.15252/emmm.202013191

Pubmed: 33544398

Kontakt

Institut für Virologie

Robert-von-Ostertag-Str. 7-13
14163 Berlin
+49 30 838 51833
virologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

SARS-CoV-2, the agent that causes COVID-19, invades epithelial cells, including those of the respiratory and gastrointestinal mucosa, using angiotensin-converting enzyme-2 (ACE2) as a receptor. Subsequent inflammation can promote rapid virus clearance, but severe cases of COVID-19 are characterized by an inefficient immune response that fails to clear the infection. Using primary epithelial organoids from human colon, we explored how the central antiviral mediator IFN-γ, which is elevated in COVID-19, affects epithelial cell differentiation, ACE2 expression, and susceptibility to infection with SARS-CoV-2. In mouse and human colon, ACE2 is mainly expressed by surface enterocytes. Inducing enterocyte differentiation in organoid culture resulted in increased ACE2 production. IFN-γ treatment promoted differentiation into mature KRT20+ enterocytes expressing high levels of ACE2, increased susceptibility to SARS-CoV-2 infection, and resulted in enhanced virus production in infected cells. Similarly, infection-induced epithelial interferon signaling promoted enterocyte maturation and enhanced ACE2 expression. We here reveal a mechanism by which IFN-γ-driven inflammatory responses induce a vulnerable epithelial state with robust replication of SARS-CoV-2, which may have an impact on disease outcome and virus transmission.