Heterogeneous Infectivity and Pathogenesis of SARS-CoV-2 Variants Beta, Delta and Omicron in Transgenic K18-hACE2 and Wildtype Mice

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 infect...

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Detalles Bibliográficos
Autores: Tarrés-Freixas, Ferran, Trinité, Benjamin, Pons-Grífols, Anna, Romero-Durana, Miguel, Riveira-Muñoz, Eva, Ávila-Nieto, Carlos, Pérez, Mónica, Garcia-Vidal, Edurne, Perez-Zsolt, Daniel, Muñoz-Basagoiti, Jordana, Raïch-Regué, Dàlia, Izquierdo-Useros, Nuria, Andrés, Cristina, Antón, Andrés, Pumarola, Tomàs, Blanco, Ignacio, Noguera-Julián, Marc, Guallar, Victor, Lepore, Rosalba, Valencia, Alfonso, Urrea, Victor, Serra Gironella, Joan, Clotet, Bonaventura, Ballana, Ester, Carrillo, Jorge, Segalés, Joaquim, Blanco, Julià
Tipo de recurso: artículo
Fecha de publicación:2022
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:20.500.12327/1813
Acceso en línea:http://hdl.handle.net/20.500.12327/1813
https://doi.org/10.3389/fmicb.2022.840757
Access Level:acceso abierto
Palabra clave:619
Descripción
Sumario: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.

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