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Generation and Application of a Luciferase Reporter Virus Based on Yellow Fever Virus 17D

  • RESEARCH ARTICLE
  • Published:
Virologica Sinica

Abstract

Yellow fever virus (YFV) is a re-emerging virus that can cause life-threatening yellow fever disease in humans. Despite the availability of an effective vaccine, little is known about the replication mechanism of YFV, and there are still no available specific anti-YFV medicines. Herein, by introducing the Renilla luciferase gene (Rluc) into an infectious clone of YFV vaccine strain 17D, we generated a recombinant virus 17D-Rluc.2A via reverse genetics approaches. The 17D-Rluc.2A had similar plaque morphology and comparable in vitro growth characteristics with its parental strain. Importantly, the reporter luciferase was efficiently expressed in 17D-Rluc.2A-infected mammalian and mosquito cells, and there was a good linear correlation between intracellular luciferase expression and extracellular infectious virion reproduction. Furthermore, by a combination of the 17D-Rluc.2A reporter virus and selective 2′-hydroxyl acylation analyzed by primer extension (SHAPE) technology, the conserved 5′-SLA element was shown to be essential for YFV replication, highlighting the capability of 17D-Rluc.2A in the investigation of YFV replication. At last, we demonstrated that two compounds with distinct anti-viral mechanisms can effectively inhibit the viral propagation in 17D-Rluc.2A-infected cells, demonstrating its potential application in the evaluation of anti-viral medicines. Taken together, the 17D-Rluc.2A serves as a useful tool for the study of YFV replication and anti-YFV medicine development.

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Acknowledgements

The authors thank for Professor Charles M. Rice from Rockefeller University for the kindly sharing of the infectious clone of 17D vaccine strain. We are grateful for the helpful discussions with Professor Pei Xu of School of Medicine, Sun Yat-sen University, and Professor Guang-Chuan Wang of the Center for Excellence in Molecular Cell Science, CAS. We thank for Professor Hua Zhang, School of Medicine, Sun Yat-sen University for the providing of the A549 cell line. This work is supported by the National Natural Science Foundation of China (81871632 and 32070183), the Natural Science Foundation of Guangdong Province (2020A1515010656), and the Creative Research Group Foster Project of the Sun Yat-sen University. Professor Zhong-Yu Liu is supported by the One-Hundred People Project of the Sun Yat-sen University.

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Authors and Affiliations

  1. The Centre for Infection and Immunity Studies, School of Medicine, Sun Yat-Sen University, Guangzhou, 510006, China

    Dan Li, Jing-Long Ye & Zhong-Yu Liu

Authors
  1. Dan Li
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  2. Jing-Long Ye
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  3. Zhong-Yu Liu
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Contributions

ZYL proposed the project. ZYL and DL designed the experiments. DL and JLY performed the experiments. ZYL and DL analyzed and interpreted the data. DL and ZYL wrote the manuscript. All authors read and confirmed the submission of the paper.

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Correspondence to Zhong-Yu Liu.

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The authors declare that they have no conflict of interest.

Animal and Human Rights Statement

This article does not contain any studies with human or animal subjects performed by any of the authors.

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Li, D., Ye, JL. & Liu, ZY. Generation and Application of a Luciferase Reporter Virus Based on Yellow Fever Virus 17D. Virol. Sin. 36, 1456–1464 (2021). https://doi.org/10.1007/s12250-021-00428-1

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  • DOI: https://doi.org/10.1007/s12250-021-00428-1

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