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SARS-CoV-2 Variants of Concern Infect the Respiratory Tract and Induce Inflammatory Response in Wild-Type Laboratory Mice

The emergence of new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants of concern pose a major threat to public health, due to possible enhanced virulence, transmissibility and immune escape. These variants may also adapt to new hosts, in part through mutations in the spike prote...

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Autores principales: Stone, Shannon, Rothan, Hussin Alwan, Natekar, Janhavi Prasad, Kumari, Pratima, Sharma, Shaligram, Pathak, Heather, Arora, Komal, Auroni, Tabassum Tasnim, Kumar, Mukesh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8777867/
https://www.ncbi.nlm.nih.gov/pubmed/35062231
http://dx.doi.org/10.3390/v14010027
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author Stone, Shannon
Rothan, Hussin Alwan
Natekar, Janhavi Prasad
Kumari, Pratima
Sharma, Shaligram
Pathak, Heather
Arora, Komal
Auroni, Tabassum Tasnim
Kumar, Mukesh
author_facet Stone, Shannon
Rothan, Hussin Alwan
Natekar, Janhavi Prasad
Kumari, Pratima
Sharma, Shaligram
Pathak, Heather
Arora, Komal
Auroni, Tabassum Tasnim
Kumar, Mukesh
author_sort Stone, Shannon
collection PubMed
description The emergence of new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants of concern pose a major threat to public health, due to possible enhanced virulence, transmissibility and immune escape. These variants may also adapt to new hosts, in part through mutations in the spike protein. In this study, we evaluated the infectivity and pathogenicity of SARS-CoV-2 variants of concern in wild-type C57BL/6 mice. Six-week-old mice were inoculated intranasally with a representative virus from the original B.1 lineage, or the emerging B.1.1.7 and B.1.351 lineages. We also infected a group of mice with a mouse-adapted SARS-CoV-2 (MA10). Viral load and mRNA levels of multiple cytokines and chemokines were analyzed in the lung tissues on day 3 after infection. Our data show that unlike the B.1 virus, the B.1.1.7 and B.1.351 viruses are capable of infecting C57BL/6 mice and replicating at high concentrations in the lungs. The B.1.351 virus replicated to higher titers in the lungs compared with the B.1.1.7 and MA10 viruses. The levels of cytokines (IL-6, TNF-α, IL-1β) and chemokine (CCL2) were upregulated in response to the B.1.1.7 and B.1.351 infection in the lungs. In addition, robust expression of viral nucleocapsid protein and histopathological changes were detected in the lungs of B.1.351-infected mice. Overall, these data indicate a greater potential for infectivity and adaptation to new hosts by emerging SARS-CoV-2 variants.
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spelling pubmed-87778672022-01-22 SARS-CoV-2 Variants of Concern Infect the Respiratory Tract and Induce Inflammatory Response in Wild-Type Laboratory Mice Stone, Shannon Rothan, Hussin Alwan Natekar, Janhavi Prasad Kumari, Pratima Sharma, Shaligram Pathak, Heather Arora, Komal Auroni, Tabassum Tasnim Kumar, Mukesh Viruses Brief Report The emergence of new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants of concern pose a major threat to public health, due to possible enhanced virulence, transmissibility and immune escape. These variants may also adapt to new hosts, in part through mutations in the spike protein. In this study, we evaluated the infectivity and pathogenicity of SARS-CoV-2 variants of concern in wild-type C57BL/6 mice. Six-week-old mice were inoculated intranasally with a representative virus from the original B.1 lineage, or the emerging B.1.1.7 and B.1.351 lineages. We also infected a group of mice with a mouse-adapted SARS-CoV-2 (MA10). Viral load and mRNA levels of multiple cytokines and chemokines were analyzed in the lung tissues on day 3 after infection. Our data show that unlike the B.1 virus, the B.1.1.7 and B.1.351 viruses are capable of infecting C57BL/6 mice and replicating at high concentrations in the lungs. The B.1.351 virus replicated to higher titers in the lungs compared with the B.1.1.7 and MA10 viruses. The levels of cytokines (IL-6, TNF-α, IL-1β) and chemokine (CCL2) were upregulated in response to the B.1.1.7 and B.1.351 infection in the lungs. In addition, robust expression of viral nucleocapsid protein and histopathological changes were detected in the lungs of B.1.351-infected mice. Overall, these data indicate a greater potential for infectivity and adaptation to new hosts by emerging SARS-CoV-2 variants. MDPI 2021-12-24 /pmc/articles/PMC8777867/ /pubmed/35062231 http://dx.doi.org/10.3390/v14010027 Text en © 2021 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 Brief Report
Stone, Shannon
Rothan, Hussin Alwan
Natekar, Janhavi Prasad
Kumari, Pratima
Sharma, Shaligram
Pathak, Heather
Arora, Komal
Auroni, Tabassum Tasnim
Kumar, Mukesh
SARS-CoV-2 Variants of Concern Infect the Respiratory Tract and Induce Inflammatory Response in Wild-Type Laboratory Mice
title SARS-CoV-2 Variants of Concern Infect the Respiratory Tract and Induce Inflammatory Response in Wild-Type Laboratory Mice
title_full SARS-CoV-2 Variants of Concern Infect the Respiratory Tract and Induce Inflammatory Response in Wild-Type Laboratory Mice
title_fullStr SARS-CoV-2 Variants of Concern Infect the Respiratory Tract and Induce Inflammatory Response in Wild-Type Laboratory Mice
title_full_unstemmed SARS-CoV-2 Variants of Concern Infect the Respiratory Tract and Induce Inflammatory Response in Wild-Type Laboratory Mice
title_short SARS-CoV-2 Variants of Concern Infect the Respiratory Tract and Induce Inflammatory Response in Wild-Type Laboratory Mice
title_sort sars-cov-2 variants of concern infect the respiratory tract and induce inflammatory response in wild-type laboratory mice
topic Brief Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8777867/
https://www.ncbi.nlm.nih.gov/pubmed/35062231
http://dx.doi.org/10.3390/v14010027
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