DOI: 10.1002/ame2.70029
Comparison of the pathogenicity of multiple SARS-CoV-2 variants in mouse models
Qi Lv1
Ming Liu2
Feifei Qi1
Mingya Liu2
Fengdi Li1
Ran Deng1
Xujian Liang1
Yanfeng Xu1
Zhiqi Song1
Yiwei Yan2
Shuyue Li2
Guocui Mou2
Linlin Bao3
1.Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious Diseases,NHC Key Laboratory of Comparative Medicine,Institute of Laboratory Animal Science,CAMS&PUMC,Beijing,China;National Center of Technology Innovation for Animal Model,Beijing,China2.Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious Diseases,NHC Key Laboratory of Comparative Medicine,Institute of Laboratory Animal Science,CAMS&PUMC,Beijing,China3.Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious Diseases,NHC Key Laboratory of Comparative Medicine,Institute of Laboratory Animal Science,CAMS&PUMC,Beijing,China;National Center of Technology Innovation for Animal Model,Beijing,China;State Key Laboratory of Respiratory Health and Multimorbidity,Beijing,China
摘要：Background:New variants of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)continue to drive global epidemics and pose significant health risks.The pathogenicity of these variants evolves under immune pressure and host factors.Understanding these changes is crucial for epidemic control and variant research.
Methods:Human angiotensin-converting enzyme 2(hACE2)transgenic mice were in-tranasally challenged with the original strain WH-09 and the variants Delta,Beta,and Omicron BA.1,while BALB/c mice were challenged with Omicron subvariants BA.5,BF.7,and XBB.1.To compare the pathogenicity differences among variants,we con-ducted a comprehensive analysis that included clinical symptom observation,meas-urement of viral loads in the trachea and lungs,evaluation of pulmonary pathology,analysis of immune cell infiltration,and quantification of cytokine levels.
Results:In hACE2 mice,the Beta variant caused significant weight loss,severe lung inflammation,increased inflammatory and chemotactic factor secretion,greater mac-rophage and neutrophil infiltration in the lungs,and higher viral loads with prolonged shedding duration.In contrast,BA.1 showed a significant reduction in pathogenicity.The BA.5,BF.7,and XBB.1 variants were less pathogenic than the WH-09,Beta,and Delta variants when infected in BALB/c mice.This was evidenced by reduced weight loss,diminished pulmonary pathology,decreased secretion of inflammatory factors and chemokines,reduced macrophage and neutrophil infiltration,as well as lower viral loads in both the trachea and lungs.
Conclusion:In hACE2 mice,the Omicron variant demonstrated the lowest pathogenic-ity,while the Beta variant exhibited the highest.Pathogenicity of the Delta variant was comparable to the original WH-09 strain.Among BALB/c mice,Omicron subvari-ants BA.5,BF.7,and XBB.1 showed no statistically significant differences in virulence.
机标关键词：sars-cov-2modelsmousecomparisonmultiplepathogenicityvariants
论文发表日期：2025-07-30
在线出版日期：2025-09-28（本平台首次上网日期，不代表文献的发表时间）
页数：11( 1302-1312 )
英文信息