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在C3H/HeJ小鼠中建立鹿蜱病毒感染模型以模拟人类临床结果。

Development of a Deer Tick Virus Infection Model in C3H/HeJ Mice to Mimic Human Clinical Outcomes.

作者信息

Paine Dakota N, Reynolds Erin S, Hart Charles E, Crooker Jessica, Thangamani Saravanan

机构信息

Department of Microbiology and Immunology, SUNY Upstate Medical University, Syracuse, NY 13210, USA.

SUNY Center for Vector-Borne Diseases, SUNY Upstate Medical University, Syracuse, NY 13210, USA.

出版信息

Viruses. 2025 Aug 7;17(8):1092. doi: 10.3390/v17081092.

DOI:10.3390/v17081092
PMID:40872806
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12390672/
Abstract

Deer tick virus (DTV) is a Tick-Borne Orthoflavivirus endemic to the United States, transmitted to humans through bites from the deer tick, , which is also the primary vector of , the causative agent of Lyme disease. Human infection with DTV can result in acute febrile illness followed by central nervous system complications, such as encephalitis and meningoencephalitis. Currently, there are mouse models established for investigating the pathogenesis and clinical outcomes of DTV that mimic human infections, but the strains of mice utilized are refractory to infection with Here, we describe the pathogenesis and clinical outcomes of DTV infection in C3H/HeJ mice. Neurological clinical signs, mortality, and weight loss were observed in all DTV-infected mice during the investigation. Infected animals demonstrated consistent viral infection in their organs. Additionally, neuropathology of brain sections indicated the presence of meningoencephalitis throughout the brain. This data, along with the clinical outcomes for the mice, indicates successful infection and showcases the neuroinvasive nature of the virus. This is the first study to identify C3H/HeJ mice as an appropriate model for DTV infection. As C3H/HeJ mice are already an established model for infection, this model could serve as an ideal system for investigating disease progression and pathogenesis of co-infections.

摘要

鹿蜱病毒(DTV)是一种在美国流行的蜱传正黄病毒,通过鹿蜱叮咬传播给人类,鹿蜱也是莱姆病病原体伯氏疏螺旋体的主要传播媒介。人类感染DTV可导致急性发热性疾病,随后出现中枢神经系统并发症,如脑炎和脑膜脑炎。目前,已建立了用于研究模拟人类感染的DTV发病机制和临床结果的小鼠模型,但所使用的小鼠品系对伯氏疏螺旋体感染具有抗性。在此,我们描述了C3H/HeJ小鼠感染DTV的发病机制和临床结果。在研究过程中,所有感染DTV的小鼠均出现神经临床症状、死亡和体重减轻。受感染动物的器官中呈现出持续的病毒感染。此外,脑切片的神经病理学检查表明全脑存在脑膜脑炎。这些数据以及小鼠的临床结果表明感染成功,并展示了该病毒的神经侵袭性。这是第一项将C3H/HeJ小鼠确定为DTV感染合适模型的研究。由于C3H/HeJ小鼠已经是伯氏疏螺旋体感染的既定模型,该模型可作为研究共感染疾病进展和发病机制的理想系统。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/447a/12390672/5827fae6b141/viruses-17-01092-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/447a/12390672/5fa3d27a7508/viruses-17-01092-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/447a/12390672/52c1f5721c50/viruses-17-01092-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/447a/12390672/5827fae6b141/viruses-17-01092-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/447a/12390672/5fa3d27a7508/viruses-17-01092-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/447a/12390672/52c1f5721c50/viruses-17-01092-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/447a/12390672/5827fae6b141/viruses-17-01092-g003.jpg

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Co-infection dynamics of and TBEV in C3H mice: insights and implications for future research.和 TBEV 在 C3H 小鼠中的共感染动力学:对未来研究的启示和影响。
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Comparative Pathogenesis of Two Lineages of Powassan Virus Reveals Distinct Clinical Outcome, Neuropathology, and Inflammation.
两种派伊山病毒株的比较发病机制揭示了不同的临床结果、神经病理学和炎症。
Viruses. 2024 May 22;16(6):820. doi: 10.3390/v16060820.
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Exploring the Susceptibility of C3H Mice to Tick-Borne Encephalitis Virus Infection: Implications for Co-Infection Models and Understanding of the Disease.探讨 C3H 小鼠对蜱传脑炎病毒感染的易感性:对共感染模型和疾病理解的意义。
Viruses. 2023 Nov 17;15(11):2270. doi: 10.3390/v15112270.
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iScience. 2023 Oct 14;26(11):108217. doi: 10.1016/j.isci.2023.108217. eCollection 2023 Nov 17.
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Infection with Increases the Replication and Dissemination of Coinfecting Powassan Virus in Ticks.感染 会增加 tick 中 Coinfecting Powassan 病毒的复制和传播。
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