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Gewählte Publikation:

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Publikationstyp: Zeitschriftenaufsatz
Dokumentart: Originalarbeit

Publikationsjahr: 2019

AutorInnen: Lercher, A; Bhattacharya, A; Popa, AM; Caldera, M; Schlapansky, MF; Baazim, H; Agerer, B; Gürtl, B; Kosack, L; Májek, P; Brunner, JS; Vitko, D; Pinter, T; Genger, JW; Orlova, A; Pikor, N; Reil, D; Ozsvár-Kozma, M; Kalinke, U; Ludewig, B; Moriggl, R; Bennett, KL; Menche, J; Cheng, PN; Schabbauer, G; Trauner, M; Klavins, K; Bergthaler, A

Titel: Type I Interferon Signaling Disrupts the Hepatic Urea Cycle and Alters Systemic Metabolism to Suppress T Cell Function.

Quelle: Immunity. 2019;



Autor/innen der Vetmeduni Vienna:

Moriggl Richard
Orlova Anna

Beteiligte Vetmed-Organisationseinheiten
Institut für Tierzucht und Genetik, Abteilung für Funktionelle Krebsgenomik


Abstract:
Infections induce complex host responses linked to antiviral defense, inflammation, and tissue damage and repair. We hypothesized that the liver, as a central metabolic hub, may orchestrate systemic metabolic changes during infection. We infected mice with chronic lymphocytic choriomeningitis virus (LCMV), performed RNA sequencing and proteomics of liver tissue, and integrated these data with serum metabolomics at different infection phases. Widespread reprogramming of liver metabolism occurred early after infection, correlating with type I interferon (IFN-I) responses. Viral infection induced metabolic alterations of the liver that depended on the interferon alpha/beta receptor (IFNAR1). Hepatocyte-intrinsic IFNAR1 repressed the transcription of metabolic genes, including Otc and Ass1, which encode urea cycle enzymes. This led to decreased arginine and increased ornithine concentrations in the circulation, resulting in suppressed virus-specific CD8


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