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野生型、P.1 和 Delta SARS-CoV-2 变异株在 K18-hACE2 转基因小鼠中的毒力特征。

Virulence Profiles of Wild-Type, P.1 and Delta SARS-CoV-2 Variants in K18-hACE2 Transgenic Mice.

机构信息

Laboratory of Cellular and Molecular Immunopathology of Malaria, Department of Clinical and Toxicological Analysis, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo 05508-000, Brazil.

Laboratory of Malaria Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, Brazil.

出版信息

Viruses. 2023 Apr 19;15(4):999. doi: 10.3390/v15040999.

DOI:10.3390/v15040999
PMID:37112979
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10146242/
Abstract

Since December 2019, the world has been experiencing the COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and we now face the emergence of several variants. We aimed to assess the differences between the wild-type (Wt) (Wuhan) strain and the P.1 (Gamma) and Delta variants using infected K18-hACE2 mice. The clinical manifestations, behavior, virus load, pulmonary capacity, and histopathological alterations were analyzed. The P.1-infected mice showed weight loss and more severe clinical manifestations of COVID-19 than the Wt and Delta-infected mice. The respiratory capacity was reduced in the P.1-infected mice compared to the other groups. Pulmonary histological findings demonstrated that a more aggressive disease was generated by the P.1 and Delta variants compared to the Wt strain of the virus. The quantification of the SARS-CoV-2 viral copies varied greatly among the infected mice although it was higher in P.1-infected mice on the day of death. Our data revealed that K18-hACE2 mice infected with the P.1 variant develop a more severe infectious disease than those infected with the other variants, despite the significant heterogeneity among the mice.

摘要

自 2019 年 12 月以来,世界一直在经历由严重急性呼吸系统综合征冠状病毒 2(SARS-CoV-2)引起的 COVID-19 大流行,而我们现在面临着几种变体的出现。我们旨在使用感染 K18-hACE2 的小鼠评估野生型(Wt)(武汉)株与 P.1(Gamma)和 Delta 变体之间的差异。分析了临床表现、行为、病毒载量、肺容量和组织病理学改变。与 Wt 和 Delta 感染的小鼠相比,P.1 感染的小鼠体重减轻,COVID-19 的临床表现更严重。与其他组相比,P.1 感染的小鼠呼吸能力降低。肺部组织学研究结果表明,与病毒的 Wt 株相比,P.1 和 Delta 变体引起了更具攻击性的疾病。尽管在死亡当天 P.1 感染的小鼠中的 SARS-CoV-2 病毒拷贝数更高,但感染的小鼠之间的病毒拷贝数存在很大差异。我们的数据表明,与其他变体感染的小鼠相比,感染 P.1 变体的 K18-hACE2 小鼠会发展出更严重的传染病,尽管小鼠之间存在很大的异质性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1a5/10146242/b8e18ca2052f/viruses-15-00999-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1a5/10146242/1b8aadf40192/viruses-15-00999-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1a5/10146242/2bfdb1c7de4e/viruses-15-00999-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1a5/10146242/ce0609470f58/viruses-15-00999-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1a5/10146242/b8e18ca2052f/viruses-15-00999-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1a5/10146242/1b8aadf40192/viruses-15-00999-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1a5/10146242/2bfdb1c7de4e/viruses-15-00999-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1a5/10146242/ce0609470f58/viruses-15-00999-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1a5/10146242/b8e18ca2052f/viruses-15-00999-g004.jpg

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