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SARS-CoV-2 variants of concern display enhanced intrinsic pathogenic properties and expanded organ tropism in mouse models

SARS-CoV-2 variants of concern (VOCs) display enhanced transmissibility and resistance to antibody neutralization. Comparing the early 2020 isolate EU-1 to the VOCs Alpha, Beta, and Gamma in mice transgenic for human ACE2 reveals that VOCs induce a broadened scope of symptoms, expand systemic infect...

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Hauptverfasser: Stolp-Rastätter, Bettina (VerfasserIn) , Stern, Marcel (VerfasserIn) , Ambiel, Ina (VerfasserIn) , Hofmann, Katharina (VerfasserIn) , Morath, Katharina (VerfasserIn) , Gallucci, Lara (VerfasserIn) , Cortese, Mirko (VerfasserIn) , Bartenschlager, Ralf (VerfasserIn) , Ruggieri, Alessia (VerfasserIn) , Graw, Frederik (VerfasserIn) , Rudelius, Martina (VerfasserIn) , Keppler, Oliver Till (VerfasserIn) , Fackler, Oliver Till (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: February 15, 2022
In: Cell reports
Year: 2022, Jahrgang: 38, Heft: 7, Pages: 1-13, e1-e5
ISSN:2211-1247
DOI:10.1016/j.celrep.2022.110387
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.celrep.2022.110387
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S2211124722001085
Volltext
Verfasserangaben:Bettina Stolp, Marcel Stern, Ina Ambiel, Katharina Hofmann, Katharina Morath, Lara Gallucci, Mirko Cortese, Ralf Bartenschlager, Alessia Ruggieri, Frederik Graw, Martina Rudelius, Oliver Till Keppler and Oliver Till Fackler
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Zusammenfassung:SARS-CoV-2 variants of concern (VOCs) display enhanced transmissibility and resistance to antibody neutralization. Comparing the early 2020 isolate EU-1 to the VOCs Alpha, Beta, and Gamma in mice transgenic for human ACE2 reveals that VOCs induce a broadened scope of symptoms, expand systemic infection to the gastrointestinal tract, elicit the depletion of natural killer cells, and trigger variant-specific cytokine production patterns. Gamma infections result in accelerated disease progression associated with increased immune activation and inflammation. All four SARS-CoV-2 variants induce pDC depletion in the lungs, paralleled by reduced interferon responses. Remarkably, VOCs also use the murine ACE2 receptor for infection to replicate in the lungs of wild-type animals, which induce cellular and innate immune responses that apparently curtail the spread of overt disease. VOCs thus display distinct intrinsic pathogenic properties with broadened tissue and host range. The enhanced pathogenicity of VOCs and their potential for reverse zoonotic transmission pose challenges to clinical and pandemic management.
Beschreibung:Gesehen am 28.03.2022
Beschreibung:Online Resource
ISSN:2211-1247
DOI:10.1016/j.celrep.2022.110387

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