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Volume 39 Issue 3
June 2024
    Citation: Shi-Zhe Xie, Ke Yao, Bei Li, Cheng Peng, Xing-Lou Yang, Zheng-Li Shi. Development of a Měnglà virus minigenome and comparison of its polymerase complexes with those of other filoviruses .VIROLOGICA SINICA, 2024, 39(3) : 459-468.  http://dx.doi.org/10.1016/j.virs.2024.03.011
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    Development of a Měnglà virus minigenome and comparison of its polymerase complexes with those of other filoviruses

    • a. State Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China;

    • b. University of Chinese Academy of Sciences, Beijing, 100049, China;

    • c. Yunnan Key Laboratory of Biodiversity Information, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650201, China;

    • d. Hubei Jiangxia Laboratory, Wuhan, 430200, China

    • Ebola virus (EBOV) and Marburg virus (MARV), members of the Filoviridae family, are highly pathogenic and can cause hemorrhagic fevers, significantly impacting human society. Bats are considered reservoirs of these viruses because related filoviruses have been discovered in bats. However, due to the requirement for maximum containment laboratories when studying infectious viruses, the characterization of bat filoviruses often relies on pseudoviruses and minigenome systems. In this study, we used RACE technology to sequence the 3′-leader and 5′-trailer of Měnglà virus (MLAV) and constructed a minigenome. Similar to MARV, the transcription activities of the MLAV minigenome are independent of VP30. We further assessed the effects of polymorphisms at the 5′ end on MLAV minigenome activity and identified certain mutations that decrease minigenome reporter efficiency, probably due to alterations in the RNA secondary structure. The reporter activity upon recombination of the 3′-leaders and 5′-trailers of MLAV, MARV, and EBOV with those of the homologous or heterologous minigenomes was compared and it was found that the polymerase complex and leader and trailer sequences exhibit intrinsic specificities. Additionally, we investigated whether the polymerase complex proteins from EBOV and MARV support MLAV minigenome RNA synthesis and found that the homologous system is more efficient than the heterologous system. Remdesivir efficiently inhibited MLAV as well as EBOV replication. In summary, this study provides new information on bat filoviruses and the minigenome will be a useful tool for high-throughput antiviral drug screening.
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      Development of a Měnglà virus minigenome and comparison of its polymerase complexes with those of other filoviruses

        Corresponding author: Xing-Lou Yang, yangxinglou@mail.kiz.ac.cn
        Corresponding author: Zheng-Li Shi, zlshi@wh.iov.cn
      • a. State Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China;
      • b. University of Chinese Academy of Sciences, Beijing, 100049, China;
      • c. Yunnan Key Laboratory of Biodiversity Information, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650201, China;
      • d. Hubei Jiangxia Laboratory, Wuhan, 430200, China
      • Received Date: 06 December 2023
      • Accepted Date: 25 March 2024

      Abstract: Ebola virus (EBOV) and Marburg virus (MARV), members of the Filoviridae family, are highly pathogenic and can cause hemorrhagic fevers, significantly impacting human society. Bats are considered reservoirs of these viruses because related filoviruses have been discovered in bats. However, due to the requirement for maximum containment laboratories when studying infectious viruses, the characterization of bat filoviruses often relies on pseudoviruses and minigenome systems. In this study, we used RACE technology to sequence the 3′-leader and 5′-trailer of Měnglà virus (MLAV) and constructed a minigenome. Similar to MARV, the transcription activities of the MLAV minigenome are independent of VP30. We further assessed the effects of polymorphisms at the 5′ end on MLAV minigenome activity and identified certain mutations that decrease minigenome reporter efficiency, probably due to alterations in the RNA secondary structure. The reporter activity upon recombination of the 3′-leaders and 5′-trailers of MLAV, MARV, and EBOV with those of the homologous or heterologous minigenomes was compared and it was found that the polymerase complex and leader and trailer sequences exhibit intrinsic specificities. Additionally, we investigated whether the polymerase complex proteins from EBOV and MARV support MLAV minigenome RNA synthesis and found that the homologous system is more efficient than the heterologous system. Remdesivir efficiently inhibited MLAV as well as EBOV replication. In summary, this study provides new information on bat filoviruses and the minigenome will be a useful tool for high-throughput antiviral drug screening.

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