A surrogate BSL2-compliant infection model recapitulating key aspects of human Marburg virus disease.

IF 8.4 2区医学 Q1 IMMUNOLOGY

Emerging Microbes & Infections Pub Date : 2025-12-01 Epub Date: 2025-01-12 DOI:10.1080/22221751.2024.2449083

Wanying Yang, Wujie Zhou, Bo Liang, Xiaojun Hu, Shen Wang, Zhenshan Wang, Tiecheng Wang, Xianzhu Xia, Na Feng, Yongkun Zhao, Feihu Yan

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引用次数: 0

Abstract

Marburg virus disease (MVD) is a severe infectious disease caused by the Marburg virus (MARV), posing a significant threat to humans. MARV needs to be operated under strict biosafety Level 4 (BSL-4) laboratory conditions. Therefore, accessible and practical animal models are urgently needed to advance prophylactic and therapeutic strategies for MARV. In this study, we constructed a recombinant vesicular stomatitis virus (VSV) expressing the Marburg virus glycoprotein (VSV-MARV/GP). Syrian hamsters infected with VSV-MARV/GP presented symptoms such as thrombocytopenia, lymphopenia, haemophilia, and multiorgan failure, developing a severe systemic disease akin to that observed in human MARV patients. Notably, the pathogenicity was found to be species-specific, age-related, sex-associated, and challenge route-dependent. Subsequently, the therapeutic efficacy of the MR191 monoclonal antibody was validated in this model. In summary, this alternative model is an effective tool for rapidly screening medical countermeasures against MARV GP in vivo under BSL-2 conditions.

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再现人类马尔堡病毒病关键方面的符合bsl2的替代感染模型

马尔堡病毒病（MVD）是由马尔堡病毒（MARV）引起的以发热和大出血为特征的严重传染病，死亡率可达90%，对人类构成重大威胁。MARV的关键在于它被归类为生物安全4级（BSL-4）病原体，这需要严格的实验条件和大量的资金。因此，迫切需要可获得和实用的动物模型来推进MARV的预防和治疗策略。本研究构建了表达马尔堡病毒糖蛋白（VSV- marv /GP）的重组水疱性口炎病毒（VSV），并利用其作为替代物诱导仓鼠致死性感染。感染VSV-MARV/GP的叙利亚仓鼠表现出血小板减少、淋巴细胞减少、血友病和多器官衰竭等症状，发展为与人类MARV患者类似的严重系统性疾病，所有动物在感染后2至3天死于感染（dpi）。值得注意的是，VSV-MARV/GP的致病性具有物种特异性、年龄相关性、性别相关性和攻毒途径依赖性。随后，在该模型中验证了MR191单克隆抗体的治疗效果。总之，该替代模型是在BSL-2条件下快速筛选体内MARV GP医学对策的有效工具。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Emerging Microbes & Infections IMMUNOLOGY-MICROBIOLOGY

CiteScore

26.20

自引率

2.30%

发文量

276

审稿时长

20 weeks

期刊介绍： Emerging Microbes & Infections is a peer-reviewed, open-access journal dedicated to publishing research at the intersection of emerging immunology and microbiology viruses. The journal's mission is to share information on microbes and infections, particularly those gaining significance in both biological and clinical realms due to increased pathogenic frequency. Emerging Microbes & Infections is committed to bridging the scientific gap between developed and developing countries. This journal addresses topics of critical biological and clinical importance, including but not limited to: - Epidemic surveillance - Clinical manifestations - Diagnosis and management - Cellular and molecular pathogenesis - Innate and acquired immune responses between emerging microbes and their hosts - Drug discovery - Vaccine development research Emerging Microbes & Infections invites submissions of original research articles, review articles, letters, and commentaries, fostering a platform for the dissemination of impactful research in the field.