Heterogeneous Infectivity and Pathogenesis of SARS-CoV-2 Variants Beta, Delta and Omicron in Transgenic K18-hACE2 and Wildtype Mice
2022
Ferran Tarrés-Freixas | Benjamin Trinité | Anna Pons-Grífols | Miguel Romero-Durana | Eva Riveira-Muñoz | Carlos Ávila-Nieto | Mónica Pérez | Mónica Pérez | Edurne Garcia-Vidal | Daniel Perez-Zsolt | Jordana Muñoz-Basagoiti | Dàlia Raïch-Regué | Nuria Izquierdo-Useros | Nuria Izquierdo-Useros | Nuria Izquierdo-Useros | Cristina Andrés | Andrés Antón | Tomàs Pumarola | Ignacio Blanco | Marc Noguera-Julián | Marc Noguera-Julián | Marc Noguera-Julián | Victor Guallar | Victor Guallar | Rosalba Lepore | Alfonso Valencia | Alfonso Valencia | Victor Urrea | Júlia Vergara-Alert | Júlia Vergara-Alert | Bonaventura Clotet | Bonaventura Clotet | Ester Ballana | Ester Ballana | Jorge Carrillo | Jorge Carrillo | Jorge Carrillo | Joaquim Segalés | Joaquim Segalés | Julià Blanco | Julià Blanco | Julià Blanco | Julià Blanco
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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