DOI: 10.1002/ame2.70026
Comparative pathogenicity of vaccinia virus and mpox virus infections in CAST/EiJ mice:Exploring splenomegaly and transcriptomic profiles
Yongzhi Hou1
Jianrong Ma1
Baoying Huang2
Na Li1
Lin Zhu1
Ziqing Jia1
Jiasen Yang1
Jingjing Zhang1
Wenjie Tan2
Jing Xue3
1.NHC Key Laboratory of Human Disease Comparative Medicine,National Center of Technology Innovation for Animal Model,Institute of Laboratory Animal Science,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing,China2.NHC Key Laboratory of Biosafety,National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases,National Institute for Viral Disease Control and Prevention,Chinese Center for Disease Control and Prevention,Beijing,China3.NHC Key Laboratory of Human Disease Comparative Medicine,National Center of Technology Innovation for Animal Model,Institute of Laboratory Animal Science,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing,China;State Key Laboratory of Respiratory Health and Multimorbidity,Key Laboratory of Pathogen Infection Prevention and Control(Peking Union Medical College),Ministry of Education,Institute of Laboratory Animal Science,Chinese Academy of Medical Sciences,Beijing,China
摘要：Background:Vaccinia virus(VACV)and mpox virus(MPXV)belong to the ortho-poxvirus genus and share high genetic similarity,making VACV widely used in the mpox pandemic.CAST/EiJ mice have been widely used for studying orthopoxvirus infection.However,the histopathological features of CAST/EiJ mice with mpox virus(MPXV)and vaccinia virus(VACV)infections have not been fully elucidated.
Methods:Four group of CAST/EiJ mice were challenged with low-dose VACV(103 PFU,VACV-L),high-dose VACV(106 PFU,VACV-H),MPXV(106 PFU)or PBS via in-traperitoneal route,and the disease signs and body weight were monitored daily.Subsequently,viral loads and titers in the blood and spleen of CAST/EiJ mice were analyzed via qPCR and TCID50 assay.Finally,the spleen samples were analyzed for histopathological,immunohistochemical and RNA-seq.
Results:Herein,we found that VACV-L and MPXV caused splenomegaly via the intra-peritoneal route,whereas VACV-H caused rapid lethality with limited splenomegaly.Transcriptome analysis from spleen revealed significant differences in gene expres-sion between VACV-L and VACV-H groups,but the differentially expressed genes induced by splenomegaly between VACV-L and MPXV groups were highly similar.Furthermore,pathway enrichment analysis demonstrated that the VACV-L,VACV-H,and MPXV groups were all associated with the calcium,MAPK,and PI3K-Akt signal-ing pathway.Compared to the lethal infection observed in VACV-H group,the sple-nomegaly in the VACV-L and MPXV groups was characterized by extramedullary hematopoiesis and increased macrophages infiltration in the red pulp.Transcriptome analysis of the spleen demonstrated that the Wnt,tumor necrosis factor(TNF),and transforming growth factor β(TGF-β)signaling pathways may promote splenomegaly by modulating granulocyte infiltration and inflammatory responses.Compared to VACV-L group,the limited splenomegaly but lethality in VACV-H-infected mice might be associated with extensive splenic necrosis,diffuse congestion,and hemorrhage in the red pulp,as well as changes in the cGMP-PKG,Ras signaling,and Fc gamma R-mediated phagocytosis pathways.
Conclusions:Our findings systematically compared the pathogenicity of VACV and MPXV in CAST/EiJ mice,incorporating splenic transcriptome analysis to provide in-sights into the potential molecular mechanism behind orthopoxvirus-induced spleno-megaly in CAST/EiJ mice.
机标关键词：profilesviruscastmicecomparativeexploringinfectionsmpox
论文发表日期：2025-08-30
在线出版日期：2025-11-05（本平台首次上网日期，不代表文献的发表时间）
页数：11( 1376-1386 )
英文信息