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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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9114491/ https://www.ncbi.nlm.nih.gov/pubmed/35602059 http://dx.doi.org/10.3389/fmicb.2022.840757 |
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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 |
author_facet | 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 |
author_sort | Tarrés-Freixas, Ferran |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9114491 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-91144912022-05-19 Heterogeneous Infectivity and Pathogenesis of SARS-CoV-2 Variants Beta, Delta and Omicron in Transgenic K18-hACE2 and Wildtype Mice 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 Front Microbiol Microbiology 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. Frontiers Media S.A. 2022-05-04 /pmc/articles/PMC9114491/ /pubmed/35602059 http://dx.doi.org/10.3389/fmicb.2022.840757 Text en Copyright © 2022 Tarrés-Freixas, Trinité, Pons-Grífols, Romero-Durana, Riveira-Muñoz, Ávila-Nieto, Pérez, Garcia-Vidal, Perez-Zsolt, Muñoz-Basagoiti, Raïch-Regué, Izquierdo-Useros, Andrés, Antón, Pumarola, Blanco, Noguera-Julián, Guallar, Lepore, Valencia, Urrea, Vergara-Alert, Clotet, Ballana, Carrillo, Segalés and Blanco. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Microbiology 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 Heterogeneous Infectivity and Pathogenesis of SARS-CoV-2 Variants Beta, Delta and Omicron in Transgenic K18-hACE2 and Wildtype Mice |
title | Heterogeneous Infectivity and Pathogenesis of SARS-CoV-2 Variants Beta, Delta and Omicron in Transgenic K18-hACE2 and Wildtype Mice |
title_full | Heterogeneous Infectivity and Pathogenesis of SARS-CoV-2 Variants Beta, Delta and Omicron in Transgenic K18-hACE2 and Wildtype Mice |
title_fullStr | Heterogeneous Infectivity and Pathogenesis of SARS-CoV-2 Variants Beta, Delta and Omicron in Transgenic K18-hACE2 and Wildtype Mice |
title_full_unstemmed | Heterogeneous Infectivity and Pathogenesis of SARS-CoV-2 Variants Beta, Delta and Omicron in Transgenic K18-hACE2 and Wildtype Mice |
title_short | Heterogeneous Infectivity and Pathogenesis of SARS-CoV-2 Variants Beta, Delta and Omicron in Transgenic K18-hACE2 and Wildtype Mice |
title_sort | heterogeneous infectivity and pathogenesis of sars-cov-2 variants beta, delta and omicron in transgenic k18-hace2 and wildtype mice |
topic | Microbiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9114491/ https://www.ncbi.nlm.nih.gov/pubmed/35602059 http://dx.doi.org/10.3389/fmicb.2022.840757 |
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