Frontiers in Microbiology (May 2022)

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

  • 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

DOI
https://doi.org/10.3389/fmicb.2022.840757
Journal volume & issue
Vol. 13

Abstract

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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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