Author:
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,Vergara-Alert Júlia,Clotet Bonaventura,Ballana Ester,Carrillo Jorge,Segalés Joaquim,Blanco Julià
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.
Funder
Spanish Ministry of Science and Innovation
Subject
Microbiology (medical),Microbiology
Cited by
47 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献