Visualization of yellow fever virus infection in mice using a bioluminescent reporter virus

Autor: Hao-Long Dong, Hong-Jiang Wang, Zhong-Yu Liu, Qing Ye, Xiao-Ling Qin, Dan Li, Yong-Qiang Deng, Tao Jiang, Xiao-Feng Li, Cheng-Feng Qin
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Emerging Microbes and Infections, Vol 10, Iss 1, Pp 1739-1750 (2021)
Druh dokumentu: article
ISSN: 22221751
2222-1751
DOI: 10.1080/22221751.2021.1967705
Popis: Yellow fever virus (YFV) is a re-emerging flavivirus, which can lead to severe clinical manifestations and high mortality, with no specific antiviral therapies available. The live-attenuated yellow fever vaccine 17D (YF17D) has been widely used for over eighty years. However, the emergence of yellow fever vaccine-associated viscerotropic disease (YFL-AVD) and yellow fever vaccine-associated neurotropic disease (YFL-AND) raised non-negligible concerns. Additionally, the attenuation mechanism of YF17D is still unclear. Thus, the development of convenient models is crucial to understand the mechanisms behind YF17D attenuation and its adverse effects. In this work, we generated a reporter YF17D expressing nano-luciferase (NLuc). In vitro and in vivo characterization demonstrated that the NLuc-YF17D shared similar biological properties with its parental strain and the NLuc activity can reflect viral infectivity reliably. Combined with in vivo bioluminescence imaging, a series of mice models of YF17D infection was established, which will be useful for the evaluation of antiviral medicines and novel vaccine candidates. Especially, we demonstrated that intraperitoneally (i.p.) infection of NLuc-YF17D in type I interferon receptor-deficient mice A129 resulted in outcomes resembling YEL-AVD and YEL-AND, evidenced by viral replication in multiple organs and invasion of the central neuronal system. Finally, in vitro and in vivo assays based on this reporter virus were established to evaluate the antiviral activities of validated antiviral agents. In conclusion, the bioluminescent reporter virus described herein provides a powerful platform to study YF17D attenuation and vaccine-associated diseases as well as to develop novel countermeasures against YFV.
Databáze: Directory of Open Access Journals
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