Heterogeneous infectivity and pathogenesis of SARS-CoV-2 variants Beta, Delta and Omicron in transgenic K18-hACE2 and wildtype mice
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hdl:2117/371613
Tipus de documentArticle
Data publicació2022-05
EditorFrontiers Media
Condicions d'accésAccés obert
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Reconeixement 4.0 Internacional
Abstract
The emerging SARS-CoV-2 variants of concern (VOCs) may display enhanced transmissibility, more severity and/or immune evasion; however, the pathogenesis of these new VOCs in experimental SARS-CoV-2 models or the potential infection of other animal species is not completely understood. Here we infected K18-hACE2 transgenic mice with B.1, B.1.351/Beta, B.1.617.2/Delta and BA.1.1/Omicron isolates and demonstrated heterogeneous infectivity and pathogenesis. B.1.351/Beta variant was the most pathogenic, while BA.1.1/Omicron led to lower viral RNA in the absence of major visible clinical signs. In parallel, we infected wildtype (WT) mice and confirmed that, contrary to B.1 and B.1.617.2/Delta, B.1.351/Beta and BA.1.1/Omicron can infect them. Infection in WT mice coursed without major clinical signs and viral RNA was transient and undetectable in the lungs by day 7 post-infection. In silico modeling supported these findings by predicting B.1.351/Beta receptor binding domain (RBD) mutations result in an increased affinity for both human and murine ACE2 receptors, while BA.1/Omicron RBD mutations only show increased affinity for murine ACE2.
CitacióTarrés Freixas, F. [et al.]. Heterogeneous infectivity and pathogenesis of SARS-CoV-2 variants Beta, Delta and Omicron in transgenic K18-hACE2 and wildtype mice. "Frontiers in Microbiology", Maig 2022, vol. 13, 840757.
ISSN1664-302X
Versió de l'editorhttps://www.frontiersin.org/articles/10.3389/fmicb.2022.840757/full
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