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Age-dependent acquisition of pathogenicity by SARS-CoV-2 Omicron BA.5
Pathology studies of SARS-CoV-2 Omicron variants of concern (VOC) are challenged by the lack of pathogenic animal models. While Omicron BA.1 and BA.2 replicate in K18-hACE2 transgenic mice, they cause minimal to negligible morbidity and mortality, and less is known about more recent Omicron VOC. Her...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10516498/ https://www.ncbi.nlm.nih.gov/pubmed/37738347 http://dx.doi.org/10.1126/sciadv.adj1736 |
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author | Imbiakha, Brian Ezzatpour, Shahrzad Buchholz, David W. Sahler, Julie Ye, Chengjin Olarte-Castillo, Ximena A. Zou, Anna Kwas, Cole O’Hare, Katelyn Choi, Annette Adeleke, Richard Ayomide Khomandiak, Solomiia Goodman, Laura Jager, Mason C. Whittaker, Gary R. Martinez-Sobrido, Luis August, Avery Aguilar, Hector C. |
author_facet | Imbiakha, Brian Ezzatpour, Shahrzad Buchholz, David W. Sahler, Julie Ye, Chengjin Olarte-Castillo, Ximena A. Zou, Anna Kwas, Cole O’Hare, Katelyn Choi, Annette Adeleke, Richard Ayomide Khomandiak, Solomiia Goodman, Laura Jager, Mason C. Whittaker, Gary R. Martinez-Sobrido, Luis August, Avery Aguilar, Hector C. |
author_sort | Imbiakha, Brian |
collection | PubMed |
description | Pathology studies of SARS-CoV-2 Omicron variants of concern (VOC) are challenged by the lack of pathogenic animal models. While Omicron BA.1 and BA.2 replicate in K18-hACE2 transgenic mice, they cause minimal to negligible morbidity and mortality, and less is known about more recent Omicron VOC. Here, we show that in contrast to Omicron BA.1, BA.5-infected mice exhibited high levels of morbidity and mortality, correlating with higher early viral loads. Neither Omicron BA.1 nor BA.5 replicated in brains, unlike most prior VOC. Only Omicron BA.5–infected mice exhibited substantial weight loss, high pathology scores in lungs, and high levels of inflammatory cells and cytokines in bronchoalveolar lavage fluid, and 5- to 8-month-old mice exhibited 100% fatality. These results identify a rodent model for pathogenesis or antiviral countermeasure studies for circulating SARS-CoV-2 Omicron BA.5. Further, differences in morbidity and mortality between Omicron BA.1 and BA.5 provide a model for understanding viral determinants of pathogenicity. |
format | Online Article Text |
id | pubmed-10516498 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-105164982023-09-23 Age-dependent acquisition of pathogenicity by SARS-CoV-2 Omicron BA.5 Imbiakha, Brian Ezzatpour, Shahrzad Buchholz, David W. Sahler, Julie Ye, Chengjin Olarte-Castillo, Ximena A. Zou, Anna Kwas, Cole O’Hare, Katelyn Choi, Annette Adeleke, Richard Ayomide Khomandiak, Solomiia Goodman, Laura Jager, Mason C. Whittaker, Gary R. Martinez-Sobrido, Luis August, Avery Aguilar, Hector C. Sci Adv Biomedicine and Life Sciences Pathology studies of SARS-CoV-2 Omicron variants of concern (VOC) are challenged by the lack of pathogenic animal models. While Omicron BA.1 and BA.2 replicate in K18-hACE2 transgenic mice, they cause minimal to negligible morbidity and mortality, and less is known about more recent Omicron VOC. Here, we show that in contrast to Omicron BA.1, BA.5-infected mice exhibited high levels of morbidity and mortality, correlating with higher early viral loads. Neither Omicron BA.1 nor BA.5 replicated in brains, unlike most prior VOC. Only Omicron BA.5–infected mice exhibited substantial weight loss, high pathology scores in lungs, and high levels of inflammatory cells and cytokines in bronchoalveolar lavage fluid, and 5- to 8-month-old mice exhibited 100% fatality. These results identify a rodent model for pathogenesis or antiviral countermeasure studies for circulating SARS-CoV-2 Omicron BA.5. Further, differences in morbidity and mortality between Omicron BA.1 and BA.5 provide a model for understanding viral determinants of pathogenicity. American Association for the Advancement of Science 2023-09-22 /pmc/articles/PMC10516498/ /pubmed/37738347 http://dx.doi.org/10.1126/sciadv.adj1736 Text en Copyright © 2023 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (https://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. |
spellingShingle | Biomedicine and Life Sciences Imbiakha, Brian Ezzatpour, Shahrzad Buchholz, David W. Sahler, Julie Ye, Chengjin Olarte-Castillo, Ximena A. Zou, Anna Kwas, Cole O’Hare, Katelyn Choi, Annette Adeleke, Richard Ayomide Khomandiak, Solomiia Goodman, Laura Jager, Mason C. Whittaker, Gary R. Martinez-Sobrido, Luis August, Avery Aguilar, Hector C. Age-dependent acquisition of pathogenicity by SARS-CoV-2 Omicron BA.5 |
title | Age-dependent acquisition of pathogenicity by SARS-CoV-2 Omicron BA.5 |
title_full | Age-dependent acquisition of pathogenicity by SARS-CoV-2 Omicron BA.5 |
title_fullStr | Age-dependent acquisition of pathogenicity by SARS-CoV-2 Omicron BA.5 |
title_full_unstemmed | Age-dependent acquisition of pathogenicity by SARS-CoV-2 Omicron BA.5 |
title_short | Age-dependent acquisition of pathogenicity by SARS-CoV-2 Omicron BA.5 |
title_sort | age-dependent acquisition of pathogenicity by sars-cov-2 omicron ba.5 |
topic | Biomedicine and Life Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10516498/ https://www.ncbi.nlm.nih.gov/pubmed/37738347 http://dx.doi.org/10.1126/sciadv.adj1736 |
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