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SARS-CoV-2 B.1.351 (beta) variant shows enhanced infectivity in K18-hACE2 transgenic mice and expanded tropism to wildtype mice compared to B.1 variant

View ORCID ProfileFerran Tarrés-Freixas, Benjamin Trinité, Anna Pons-Grífols, Miguel Romero-Durana, Eva Riveira-Muñoz, Carlos Ávila-Nieto, Mónica Pérez, Edurne Garcia-Vidal, Daniel Pérez-Zsolt, Jordana Muñoz-Basagoiti, Dàlia Raïch-Regué, View ORCID ProfileNuria Izquierdo-Useros, Ignacio Blanco, Marc Noguera-Julián, Victor Guallar, Rosalba Lepore, Alfonso Valencia, Júlia Vergara-Alert, Bonaventura Clotet, Ester Ballana, Jorge Carrillo, Joaquim Segalés, Julià Blanco
doi: https://doi.org/10.1101/2021.08.03.454861
Ferran Tarrés-Freixas
1IrsiCaixa AIDS Research Institute, Germans Trias i Pujol Research Institute (IGTP), Can Ruti Campus, UAB, 08916, Badalona, Catalonia, Spain
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  • ORCID record for Ferran Tarrés-Freixas
Benjamin Trinité
1IrsiCaixa AIDS Research Institute, Germans Trias i Pujol Research Institute (IGTP), Can Ruti Campus, UAB, 08916, Badalona, Catalonia, Spain
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Anna Pons-Grífols
1IrsiCaixa AIDS Research Institute, Germans Trias i Pujol Research Institute (IGTP), Can Ruti Campus, UAB, 08916, Badalona, Catalonia, Spain
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Miguel Romero-Durana
2Barcelona Supercomputing Center, 08034, Barcelona, Catalonia, Spain
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Eva Riveira-Muñoz
1IrsiCaixa AIDS Research Institute, Germans Trias i Pujol Research Institute (IGTP), Can Ruti Campus, UAB, 08916, Badalona, Catalonia, Spain
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Carlos Ávila-Nieto
1IrsiCaixa AIDS Research Institute, Germans Trias i Pujol Research Institute (IGTP), Can Ruti Campus, UAB, 08916, Badalona, Catalonia, Spain
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Mónica Pérez
3IRTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA-UAB), Campus de la UAB, 08193 Bellaterra, Spain
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Edurne Garcia-Vidal
1IrsiCaixa AIDS Research Institute, Germans Trias i Pujol Research Institute (IGTP), Can Ruti Campus, UAB, 08916, Badalona, Catalonia, Spain
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Daniel Pérez-Zsolt
1IrsiCaixa AIDS Research Institute, Germans Trias i Pujol Research Institute (IGTP), Can Ruti Campus, UAB, 08916, Badalona, Catalonia, Spain
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Jordana Muñoz-Basagoiti
1IrsiCaixa AIDS Research Institute, Germans Trias i Pujol Research Institute (IGTP), Can Ruti Campus, UAB, 08916, Badalona, Catalonia, Spain
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Dàlia Raïch-Regué
1IrsiCaixa AIDS Research Institute, Germans Trias i Pujol Research Institute (IGTP), Can Ruti Campus, UAB, 08916, Badalona, Catalonia, Spain
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Nuria Izquierdo-Useros
1IrsiCaixa AIDS Research Institute, Germans Trias i Pujol Research Institute (IGTP), Can Ruti Campus, UAB, 08916, Badalona, Catalonia, Spain
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Ignacio Blanco
4Germans Trias i Pujol Hospital, 08916, Badalona, Catalonia, Spain
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Marc Noguera-Julián
1IrsiCaixa AIDS Research Institute, Germans Trias i Pujol Research Institute (IGTP), Can Ruti Campus, UAB, 08916, Badalona, Catalonia, Spain
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Victor Guallar
2Barcelona Supercomputing Center, 08034, Barcelona, Catalonia, Spain
5Catalan Institution for Research and Advanced Studies (ICREA), 08010, Barcelona, Catalonia, Spain
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Rosalba Lepore
2Barcelona Supercomputing Center, 08034, Barcelona, Catalonia, Spain
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Alfonso Valencia
2Barcelona Supercomputing Center, 08034, Barcelona, Catalonia, Spain
5Catalan Institution for Research and Advanced Studies (ICREA), 08010, Barcelona, Catalonia, Spain
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Júlia Vergara-Alert
3IRTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA-UAB), Campus de la UAB, 08193 Bellaterra, Spain
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Bonaventura Clotet
1IrsiCaixa AIDS Research Institute, Germans Trias i Pujol Research Institute (IGTP), Can Ruti Campus, UAB, 08916, Badalona, Catalonia, Spain
6University of Vic–Central University of Catalonia (UVic-UCC), 08500, Vic, Catalonia, Spain
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Ester Ballana
1IrsiCaixa AIDS Research Institute, Germans Trias i Pujol Research Institute (IGTP), Can Ruti Campus, UAB, 08916, Badalona, Catalonia, Spain
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Jorge Carrillo
1IrsiCaixa AIDS Research Institute, Germans Trias i Pujol Research Institute (IGTP), Can Ruti Campus, UAB, 08916, Badalona, Catalonia, Spain
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Joaquim Segalés
3IRTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA-UAB), Campus de la UAB, 08193 Bellaterra, Spain
7Departament de Sanitat i Anatomia Animals, Facultat de Veterinària, UAB, 08193, Bellaterra, Catalonia, Spain
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Julià Blanco
1IrsiCaixa AIDS Research Institute, Germans Trias i Pujol Research Institute (IGTP), Can Ruti Campus, UAB, 08916, Badalona, Catalonia, Spain
6University of Vic–Central University of Catalonia (UVic-UCC), 08500, Vic, Catalonia, Spain
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  • For correspondence: jblanco@irsicaixa.es
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Abstract

SARS-CoV-2 variants display enhanced transmissibility and/or immune evasion and can be generated in humans or animals, like minks, thus generating new reservoirs. The continuous surveillance of animal susceptibility to new variants is necessary to predict pandemic evolution. In this study we demonstrate that, compared to the B.1 SARS-CoV-2 variant, K18-hACE2 transgenic mice challenged with the B.1.351 variant displayed a faster progression of infection. Furthermore, we also report that B.1.351 can establish infection in wildtype mice, while B.1 cannot. B.1.351-challenged wildtype mice showed a milder infection than transgenic mice, confirmed by detectable viral loads in oropharyngeal swabs and tissues, lung pathology, immunohistochemistry and serology. In silico models supported these findings by demonstrating that the Spike mutations in B.1.351 resulted in increased affinity for both human and murine ACE2 receptors. Overall, this study highlights the plasticity of SARS-CoV-2 animal susceptibility landscape, which may contribute to viral persistence and expansion.

Competing Interest Statement

Unrelated to the submitted work, J.C., J.B., and B.C. are founders and shareholders of AlbaJuna Therapeutics, S.L; B.C. is founder and shareholder of AELIX Therapeutics, S.L.; J.B. reports institutional grants from HIPRA and MSD; N.I-U. reports institutional grants from Pharma Mar and Dentaid. The authors declare no other competing conflicts of interests.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted August 03, 2021.
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SARS-CoV-2 B.1.351 (beta) variant shows enhanced infectivity in K18-hACE2 transgenic mice and expanded tropism to wildtype mice compared to B.1 variant
Ferran Tarrés-Freixas, Benjamin Trinité, Anna Pons-Grífols, Miguel Romero-Durana, Eva Riveira-Muñoz, Carlos Ávila-Nieto, Mónica Pérez, Edurne Garcia-Vidal, Daniel Pérez-Zsolt, Jordana Muñoz-Basagoiti, Dàlia Raïch-Regué, Nuria Izquierdo-Useros, Ignacio Blanco, Marc Noguera-Julián, Victor Guallar, Rosalba Lepore, Alfonso Valencia, Júlia Vergara-Alert, Bonaventura Clotet, Ester Ballana, Jorge Carrillo, Joaquim Segalés, Julià Blanco
bioRxiv 2021.08.03.454861; doi: https://doi.org/10.1101/2021.08.03.454861
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SARS-CoV-2 B.1.351 (beta) variant shows enhanced infectivity in K18-hACE2 transgenic mice and expanded tropism to wildtype mice compared to B.1 variant
Ferran Tarrés-Freixas, Benjamin Trinité, Anna Pons-Grífols, Miguel Romero-Durana, Eva Riveira-Muñoz, Carlos Ávila-Nieto, Mónica Pérez, Edurne Garcia-Vidal, Daniel Pérez-Zsolt, Jordana Muñoz-Basagoiti, Dàlia Raïch-Regué, Nuria Izquierdo-Useros, Ignacio Blanco, Marc Noguera-Julián, Victor Guallar, Rosalba Lepore, Alfonso Valencia, Júlia Vergara-Alert, Bonaventura Clotet, Ester Ballana, Jorge Carrillo, Joaquim Segalés, Julià Blanco
bioRxiv 2021.08.03.454861; doi: https://doi.org/10.1101/2021.08.03.454861

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