ArticleAnimal models and experimental medicine2025
Comparative pathogenicity of vaccinia virus and mpox virus infections in CAST/EiJ mice: Exploring splenomegaly and transcriptomic profiles.
Article in Animal models and experimental medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- CAST/EiJ and NOG mice as lethal animal models for a 2022 human isolate of monkeypox virus Clade IIb.Scientific reports · 2026Article
- Intranasal VACV VR-1354 infection impairs chemosensory function and induces olfactory bulb neuroinflammation in mice.Frontiers in immunology · 2026Article
- From skin lesions to multi-organ involvement: Organ tropism and pathogenesis of mpox virus.iScience · 2025Review
- Comparative pathogenicity of vaccinia virus and mpox virus infections in CAST/EiJ mice: Exploring splenomegaly and transcriptomic profiles.Animal models and experimental medicine · 2025Article
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10 authors.
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Abstract
backgroundVaccinia virus (VACV) and mpox virus (MPXV) belong to the orthopoxvirus 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.
methodsFour group of CAST/EiJ mice were challenged with low-dose VACV (10
resultsHerein, we found that VACV-L and MPXV caused splenomegaly via the intraperitoneal route, whereas VACV-H caused rapid lethality with limited splenomegaly. Transcriptome analysis from spleen revealed significant differences in gene expression 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 signaling pathway. Compared to the lethal infection observed in VACV-H group, the splenomegaly 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.
conclusionsOur findings systematically compared the pathogenicity of VACV and MPXV in CAST/EiJ mice, incorporating splenic transcriptome analysis to provide insights into the potential molecular mechanism behind orthopoxvirus-induced splenomegaly in CAST/EiJ mice.
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