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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Autores: Tarrés-Freixas, Ferran|||0000-0002-1569-0126, Trinité, Benjamin|||0000-0003-3809-042X, Pons-Grífols, Anna|||0000-0002-8402-3941, Romero-Durana, Miguel|||0000-0001-6779-8553, Riveira Muñoz, Eva|||0000-0002-6396-1162, Avila-Nieto, Carlos, Pérez, Mónica, García Vidal, Edurne|||0000-0003-0698-8710, Perez-Zsolt, Daniel|||0000-0003-4192-7622, Muñoz-Basagoiti, Jordana|||0000-0002-0384-5928, Raïch-Regué, Dàlia|||0000-0001-7656-5700, Izquierdo Useros, Nuria|||0000-0002-1039-1821, Andrés, Cristina|||0000-0002-3200-0895, Antón Pagarolas, Andrés, 1976-|||0000-0002-1476-0815, Pumarola Suñé, Tomàs|||0000-0002-5171-7461, Blanco Guillermo, Ignacio|||0000-0002-7414-7481, Noguera-Julian, Marc|||0000-0002-6194-1395, Guallar, Victor|||0000-0002-4580-1114, Lepore, Rosalba, Valencia, Alfonso|||0000-0002-8937-6789, Urrea, Víctor|||0000-0002-2577-856X, Vergara-Alert, Júlia|||0000-0001-7484-444X, Clotet Sala, Bonaventura|||0000-0003-3232-4598, Ballana, Ester|||0000-0002-5215-7363, Carrillo, Jorge|||0000-0003-0221-5948, Segalés Coma, Joaquim|||0000-0002-1539-7261, Blanco, Julià|||0000-0002-2225-0217
Tipo de recurso: artículo
Fecha de publicación:2022
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:266213
Acceso en línea:https://ddd.uab.cat/record/266213
https://dx.doi.org/urn:doi:10.3389/fmicb.2022.840757
Access Level:acceso abierto
Palabra clave:SARS-CoV-2 variants of concern
ACE2
Viral load
Histology
In silico modeling
Infection
K18-hACE2 mice
Wildtype mice
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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