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

Autor: Yulong Wang, Linjin Fan, Pengfei Ye, Zequn Wang, Chudan Liang, Quan Liu, Xiaofeng Yang, Zhenyu Long, Wendi Shi, Yuandong Zhou, Jingyan Lin, Huijun Yan, Hongxin Huang, Linna Liu, Jun Qian
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Emerging Microbes and Infections, Vol 13, Iss 1 (2024)
Druh dokumentu: article
ISSN: 22221751
2222-1751
DOI: 10.1080/22221751.2024.2368217
Popis: 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.
Databáze: Directory of Open Access Journals
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