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新型转录和复制型病毒样颗粒系统模拟尼帕病毒生命周期。

Novel transcription and replication-competent virus-like particles system modelling the Nipah virus life cycle.

机构信息

Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China.

Institute of Infectious Diseases, Guangzhou Eighth people's Hospital, Guangzhou Medical University, Guangzhou, People's Republic of China.

出版信息

Emerg Microbes Infect. 2024 Dec;13(1):2368217. doi: 10.1080/22221751.2024.2368217. Epub 2024 Jul 5.

DOI:10.1080/22221751.2024.2368217
PMID:38865205
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11229746/
Abstract

Nipah virus (NiV), a highly pathogenic Henipavirus in humans, has been responsible for annual outbreaks in recent years. Experiments involving live NiV are highly restricted to biosafety level 4 (BSL-4) laboratories, which impedes NiV research. In this study, we developed transcription and replication-competent NiV-like particles (trVLP-NiV) lacking N, P, and L genes. This trVLP-NiV exhibited the ability to infect and continuously passage in cells ectopically expressing N, P, and L proteins while maintaining stable genetic characteristics. Moreover, the trVLP-NiV displayed a favourable safety profile in hamsters. Using the system, we found the NiV nucleoprotein residues interacting with viral RNA backbone affected viral replication in opposite patterns. This engineered system was sensitive to well-established antiviral drugs, innate host antiviral factors, and neutralizing antibodies. We then established a high-throughput screening platform utilizing the trVLP-NiV, leading to the identification of tunicamycin as a potential anti-NiV compound. Evidence showed that tunicamycin inhibited NiV replication by decreasing the infectivity of progeny virions. In conclusion, this trVLP-NiV system provided a convenient and versatile molecular tool for investigating NiV molecular biology and conducting antiviral drug screening under BSL-2 conditions. Its application will contribute to the development of medical countermeasures against NiV infections.

摘要

亨德拉病毒（NiV）是一种对人类具有高度致病性的亨尼帕病毒，近年来已导致每年爆发疫情。涉及活 NiV 的实验受到高度限制，只能在生物安全 4 级（BSL-4）实验室中进行，这阻碍了 NiV 的研究。在这项研究中，我们开发了缺乏 N、P 和 L 基因的转录和复制有效的 NiV 样颗粒（trVLP-NiV）。这种 trVLP-NiV 表现出感染和在异位表达 N、P 和 L 蛋白的细胞中持续传代的能力，同时保持稳定的遗传特征。此外，trVLP-NiV 在仓鼠中表现出良好的安全性。利用该系统，我们发现 NiV 核蛋白残基与病毒 RNA 骨架相互作用，以相反的模式影响病毒复制。该工程系统对已确立的抗病毒药物、先天宿主抗病毒因子和中和抗体敏感。然后，我们利用 trVLP-NiV 建立了一个高通量筛选平台，鉴定出 tunicamycin 是一种潜在的抗 NiV 化合物。证据表明，tunicamycin 通过降低病毒粒子的感染力来抑制 NiV 复制。总之，该 trVLP-NiV 系统为研究 NiV 分子生物学和在 BSL-2 条件下进行抗病毒药物筛选提供了一种方便、通用的分子工具。它的应用将有助于开发针对 NiV 感染的医疗对策。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc09/11229746/b089e51de522/TEMI_A_2368217_F0007_OC.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc09/11229746/b089e51de522/TEMI_A_2368217_F0007_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc09/11229746/296b95bdbe88/TEMI_A_2368217_F0001_OC.jpg
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