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Characterization of Three Variants of SARS-CoV-2 In Vivo Shows Host-Dependent Pathogenicity in Hamsters, While Not in K18-hACE2 Mice

Animal models are used in preclinical trials to test vaccines, antivirals, monoclonal antibodies, and immunomodulatory drug therapies against SARS-CoV-2. However, these drugs often do not produce equivalent results in human clinical trials. Here, we show how different animal models infected with som...

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Autores principales: Toomer, Gabriela, Burns, Whitney, Garcia, Liliana, Henry, Gerelyn, Biancofiori, Anthony, George, Albert, Duffy, Ciera, Chu, Justin, Sides, Morgan, Muñoz, Melissa, Garcia, Kelly, Nikolai-Yogerst, Anya, Peng, Xinjian, Westfall, Landon, Baker, Robert
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9693146/
https://www.ncbi.nlm.nih.gov/pubmed/36423193
http://dx.doi.org/10.3390/v14112584
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author Toomer, Gabriela
Burns, Whitney
Garcia, Liliana
Henry, Gerelyn
Biancofiori, Anthony
George, Albert
Duffy, Ciera
Chu, Justin
Sides, Morgan
Muñoz, Melissa
Garcia, Kelly
Nikolai-Yogerst, Anya
Peng, Xinjian
Westfall, Landon
Baker, Robert
author_facet Toomer, Gabriela
Burns, Whitney
Garcia, Liliana
Henry, Gerelyn
Biancofiori, Anthony
George, Albert
Duffy, Ciera
Chu, Justin
Sides, Morgan
Muñoz, Melissa
Garcia, Kelly
Nikolai-Yogerst, Anya
Peng, Xinjian
Westfall, Landon
Baker, Robert
author_sort Toomer, Gabriela
collection PubMed
description Animal models are used in preclinical trials to test vaccines, antivirals, monoclonal antibodies, and immunomodulatory drug therapies against SARS-CoV-2. However, these drugs often do not produce equivalent results in human clinical trials. Here, we show how different animal models infected with some of the most clinically relevant SARS-CoV-2 variants, WA1/2020, B.1.617.2/Delta, B.1.1.529/Omicron, and BA5.2/Omicron, have independent outcomes. We show that in K18-hACE2 mice, B.1.617.2 is more pathogenic, followed by WA1, while B.1.1.529 showed an absence of clinical signs. Only B.1.1.529 was able to infect C57BL/6J mice, which lack the human ACE2 receptor. B.1.1.529-infected C57BL/6J mice had different T cell profiles compared to infected K18-hACE2 mice, while viral shedding profiles and viral titers in lungs were similar between the K18-hACE2 and the C57BL/6J mice. These data suggest B.1.1.529 virus adaptation to a new host and shows that asymptomatic carriers can accumulate and shed virus. Next, we show how B.1.617.2, WA1 and BA5.2/Omicron have similar viral replication kinetics, pathogenicity, and viral shedding profiles in hamsters, demonstrating that the increased pathogenicity of B.1.617.2 observed in mice is host-dependent. Overall, these findings suggest that small animal models are useful to parallel human clinical data, but the experimental design places an important role in interpreting the data. Importance: There is a need to investigate SARS-CoV-2 variant phenotypes in different animal models due to the lack of reproducible outcomes when translating experiments to the human population. Our findings highlight the correlation of clinically relevant SARS-CoV-2 variants in animal models with human infections. Experimental design and understanding of correct animal models are essential to interpreting data to develop antivirals, vaccines, and other therapeutic compounds against COVID-19.
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spelling pubmed-96931462022-11-26 Characterization of Three Variants of SARS-CoV-2 In Vivo Shows Host-Dependent Pathogenicity in Hamsters, While Not in K18-hACE2 Mice Toomer, Gabriela Burns, Whitney Garcia, Liliana Henry, Gerelyn Biancofiori, Anthony George, Albert Duffy, Ciera Chu, Justin Sides, Morgan Muñoz, Melissa Garcia, Kelly Nikolai-Yogerst, Anya Peng, Xinjian Westfall, Landon Baker, Robert Viruses Article Animal models are used in preclinical trials to test vaccines, antivirals, monoclonal antibodies, and immunomodulatory drug therapies against SARS-CoV-2. However, these drugs often do not produce equivalent results in human clinical trials. Here, we show how different animal models infected with some of the most clinically relevant SARS-CoV-2 variants, WA1/2020, B.1.617.2/Delta, B.1.1.529/Omicron, and BA5.2/Omicron, have independent outcomes. We show that in K18-hACE2 mice, B.1.617.2 is more pathogenic, followed by WA1, while B.1.1.529 showed an absence of clinical signs. Only B.1.1.529 was able to infect C57BL/6J mice, which lack the human ACE2 receptor. B.1.1.529-infected C57BL/6J mice had different T cell profiles compared to infected K18-hACE2 mice, while viral shedding profiles and viral titers in lungs were similar between the K18-hACE2 and the C57BL/6J mice. These data suggest B.1.1.529 virus adaptation to a new host and shows that asymptomatic carriers can accumulate and shed virus. Next, we show how B.1.617.2, WA1 and BA5.2/Omicron have similar viral replication kinetics, pathogenicity, and viral shedding profiles in hamsters, demonstrating that the increased pathogenicity of B.1.617.2 observed in mice is host-dependent. Overall, these findings suggest that small animal models are useful to parallel human clinical data, but the experimental design places an important role in interpreting the data. Importance: There is a need to investigate SARS-CoV-2 variant phenotypes in different animal models due to the lack of reproducible outcomes when translating experiments to the human population. Our findings highlight the correlation of clinically relevant SARS-CoV-2 variants in animal models with human infections. Experimental design and understanding of correct animal models are essential to interpreting data to develop antivirals, vaccines, and other therapeutic compounds against COVID-19. MDPI 2022-11-21 /pmc/articles/PMC9693146/ /pubmed/36423193 http://dx.doi.org/10.3390/v14112584 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Toomer, Gabriela
Burns, Whitney
Garcia, Liliana
Henry, Gerelyn
Biancofiori, Anthony
George, Albert
Duffy, Ciera
Chu, Justin
Sides, Morgan
Muñoz, Melissa
Garcia, Kelly
Nikolai-Yogerst, Anya
Peng, Xinjian
Westfall, Landon
Baker, Robert
Characterization of Three Variants of SARS-CoV-2 In Vivo Shows Host-Dependent Pathogenicity in Hamsters, While Not in K18-hACE2 Mice
title Characterization of Three Variants of SARS-CoV-2 In Vivo Shows Host-Dependent Pathogenicity in Hamsters, While Not in K18-hACE2 Mice
title_full Characterization of Three Variants of SARS-CoV-2 In Vivo Shows Host-Dependent Pathogenicity in Hamsters, While Not in K18-hACE2 Mice
title_fullStr Characterization of Three Variants of SARS-CoV-2 In Vivo Shows Host-Dependent Pathogenicity in Hamsters, While Not in K18-hACE2 Mice
title_full_unstemmed Characterization of Three Variants of SARS-CoV-2 In Vivo Shows Host-Dependent Pathogenicity in Hamsters, While Not in K18-hACE2 Mice
title_short Characterization of Three Variants of SARS-CoV-2 In Vivo Shows Host-Dependent Pathogenicity in Hamsters, While Not in K18-hACE2 Mice
title_sort characterization of three variants of sars-cov-2 in vivo shows host-dependent pathogenicity in hamsters, while not in k18-hace2 mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9693146/
https://www.ncbi.nlm.nih.gov/pubmed/36423193
http://dx.doi.org/10.3390/v14112584
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