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建立基于伪病毒的金黄仓鼠模型用于亨德拉病毒感染的附着和进入阶段及保护性免疫评估

Establishment of a Pseudovirus-Based Golden Hamster Model for the Attachment and Entry Stages of Hendra Virus Infection and Evaluation of Protective Immunity.

作者信息

Li Tao, Liao Binfan, Li Danfeng, Zhang Jie, Zhao Chunhui, Pei Yunfei, Chen Liping, Wang Meng, Liu Yawen, Wu Xi, Huang Weijin, Nie Jianhui

机构信息

Division of HIV/AIDS and Sexually-Transmitted Virus Vaccines, Institute for Biological Product Control, National Institutes for Food and Drug Control (NIFDC), Beijing 102629, China.

State Key Laboratory of Drug Regulatory Science, Beijing 102629, China.

出版信息

Pathogens. 2025 Sep 10;14(9):910. doi: 10.3390/pathogens14090910.

DOI:10.3390/pathogens14090910
PMID:41011810
Abstract

OBJECTIVE

Establish an in vivo evaluation model focused on the attachment and entry stages of Hendra virus infection for protective immunity assessment.

METHODS

A golden hamster infection model based on recombinant Hendra-F/G pseudovirus was developed, and a luciferase luminescence assay was used to assess the optimal pseudoviral challenge in terms of route of infection, dose and detection time. The biodistribution of the pseudovirus in infected organs was evaluated using the IVIS spectral CT system. The protective effect of antibody prophylaxis was evaluated by measuring the luminescence intensity of pseudoviruses.

RESULTS

Intraperitoneal injection was identified as the optimal route of infection, and the optimal time of detection was 6 h post-challenge. Our model simulates the infection of the brain and lungs by live viruses, with the strongest infection occurring in the abdomen, especially in the intestinal organs. The dose of pseudovirus was linearly correlated with luminescence intensity. The infection model was able to differentiate the protective effect of monoclonal antibodies, with complete protection in the high-dose group.

CONCLUSIONS

The recombinant Hendra-F/G pseudovirus hamster model allows the effective evaluation of prophylactic monoclonal antibodies, providing a crucial tool for studying Hendra virus infection and control strategies.

摘要

目的

建立一种聚焦于亨德拉病毒感染的附着和进入阶段的体内评估模型,用于保护性免疫评估。

方法

构建了基于重组亨德拉 - F/G假病毒的金黄仓鼠感染模型,并使用荧光素酶发光测定法从感染途径、剂量和检测时间方面评估最佳假病毒攻击条件。使用IVIS光谱CT系统评估假病毒在受感染器官中的生物分布。通过测量假病毒的发光强度评估抗体预防的保护效果。

结果

确定腹腔注射为最佳感染途径,最佳检测时间为攻击后6小时。我们的模型模拟了活病毒对脑和肺的感染,腹部尤其是肠道器官的感染最强。假病毒剂量与发光强度呈线性相关。该感染模型能够区分单克隆抗体的保护效果,高剂量组有完全保护作用。

结论

重组亨德拉 - F/G假病毒仓鼠模型能够有效评估预防性单克隆抗体,为研究亨德拉病毒感染及控制策略提供了关键工具。

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本文引用的文献

1
A monoclonal antibody targeting conserved regions of pre-fusion protein cross-neutralizes Nipah and Hendra virus variants.一种靶向融合前蛋白保守区域的单克隆抗体可交叉中和尼帕病毒和亨德拉病毒变种。
Antiviral Res. 2025 Aug;240:106215. doi: 10.1016/j.antiviral.2025.106215. Epub 2025 Jun 18.
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Current status of diagnostic assays for emerging zoonotic viruses: Nipah and Hendra.新兴人畜共患病病毒诊断检测方法的现状:尼帕病毒和亨德拉病毒。
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Animal Models for Henipavirus Research.
动物模型在亨德拉尼帕病毒研究中的应用。
Viruses. 2023 Sep 22;15(10):1980. doi: 10.3390/v15101980.
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Establishment of a Nipah Virus Disease Model in Hamsters, including a Comparison of Intranasal and Intraperitoneal Routes of Challenge.在仓鼠中建立尼帕病毒病模型,包括鼻内和腹腔内攻毒途径的比较。
Pathogens. 2023 Jul 26;12(8):976. doi: 10.3390/pathogens12080976.
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Pseudotyped Viruses.伪型病毒。
Adv Exp Med Biol. 2023;1407:1-27. doi: 10.1007/978-981-99-0113-5_1.
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Novel variant Hendra virus genotype 2 infection in a horse in the greater Newcastle region, New South Wales, Australia.澳大利亚新南威尔士州大纽卡斯尔地区一匹马感染新型亨德拉病毒2型基因型变异株。
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A Zoonotic Henipavirus in Febrile Patients in China.中国发热患者中的一种人畜共患亨尼帕病毒
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Generating human artery and vein cells from pluripotent stem cells highlights the arterial tropism of Nipah and Hendra viruses.从多能干细胞中生成人动脉和静脉细胞突出了尼帕病毒和亨德拉病毒的动脉趋向性。
Cell. 2022 Jul 7;185(14):2523-2541.e30. doi: 10.1016/j.cell.2022.05.024. Epub 2022 Jun 22.
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