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Structural insight into arenavirus replication machinery

Author

Listed:
  • Ruchao Peng

    (Institute of Microbiology, Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Xin Xu

    (University of Chinese Academy of Sciences)

  • Jiamei Jing

    (Institute of Microbiology, Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Min Wang

    (Institute of Microbiology, Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Qi Peng

    (Institute of Microbiology, Chinese Academy of Sciences
    University of Chinese Academy of Sciences
    Shenzhen Third People’s Hospital
    Center for Influenza Research and Early-warning (CASCIRE), CAS-TWAS Center of Excellence for Emerging Infectious Disease (CEEID), Chinese Academy of Sciences)

  • Sheng Liu

    (Institute of Microbiology, Chinese Academy of Sciences)

  • Ying Wu

    (Shenzhen Third People’s Hospital
    Wuhan University)

  • Xichen Bao

    (Chinese Academy of Sciences)

  • Peiyi Wang

    (Southern University of Science and Technology)

  • Jianxun Qi

    (Institute of Microbiology, Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • George F. Gao

    (Institute of Microbiology, Chinese Academy of Sciences
    University of Chinese Academy of Sciences
    Shenzhen Third People’s Hospital
    Center for Influenza Research and Early-warning (CASCIRE), CAS-TWAS Center of Excellence for Emerging Infectious Disease (CEEID), Chinese Academy of Sciences)

  • Yi Shi

    (Institute of Microbiology, Chinese Academy of Sciences
    University of Chinese Academy of Sciences
    Shenzhen Third People’s Hospital
    Center for Influenza Research and Early-warning (CASCIRE), CAS-TWAS Center of Excellence for Emerging Infectious Disease (CEEID), Chinese Academy of Sciences)

Abstract

Arenaviruses can cause severe haemorrhagic fever and neurological diseases in humans and other animals, exemplified by Lassa mammarenavirus, Machupo mammarenavirus and lymphocytic choriomeningitis virus, posing great threats to public health1–4. These viruses encode a large multi-domain RNA-dependent RNA polymerase for transcription and replication of the viral genome5. Viral polymerases are one of the leading antiviral therapeutic targets. However, the structure of arenavirus polymerase is not yet known. Here we report the near-atomic resolution structures of Lassa and Machupo virus polymerases in both apo and promoter-bound forms. These structures display a similar overall architecture to influenza virus and bunyavirus polymerases but possess unique local features, including an arenavirus-specific insertion domain that regulates the polymerase activity. Notably, the ordered active site of arenavirus polymerase is inherently switched on, without the requirement for allosteric activation by 5′-viral RNA, which is a necessity for both influenza virus and bunyavirus polymerases6,7. Moreover, dimerization could facilitate the polymerase activity. These findings advance our understanding of the mechanism of arenavirus replication and provide an important basis for developing antiviral therapeutics.

Suggested Citation

  • Ruchao Peng & Xin Xu & Jiamei Jing & Min Wang & Qi Peng & Sheng Liu & Ying Wu & Xichen Bao & Peiyi Wang & Jianxun Qi & George F. Gao & Yi Shi, 2020. "Structural insight into arenavirus replication machinery," Nature, Nature, vol. 579(7800), pages 615-619, March.
  • Handle: RePEc:nat:nature:v:579:y:2020:i:7800:d:10.1038_s41586-020-2114-2
    DOI: 10.1038/s41586-020-2114-2
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    Citations

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    Cited by:

    1. Jun Ma & Shuangyue Zhang & Xinzheng Zhang, 2021. "Structure of Machupo virus polymerase in complex with matrix protein Z," Nature Communications, Nature, vol. 12(1), pages 1-8, December.
    2. Quentin Durieux Trouilleton & Dominique Housset & Paco Tarillon & Benoît Arragain & Hélène Malet, 2024. "Structural characterization of the oligomerization of full-length Hantaan virus polymerase into symmetric dimers and hexamers," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    3. Tomas Kouba & Dominik Vogel & Sigurdur R. Thorkelsson & Emmanuelle R. J. Quemin & Harry M. Williams & Morlin Milewski & Carola Busch & Stephan Günther & Kay Grünewald & Maria Rosenthal & Stephen Cusac, 2021. "Conformational changes in Lassa virus L protein associated with promoter binding and RNA synthesis activity," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
    4. Benoît Arragain & Quentin Durieux Trouilleton & Florence Baudin & Jan Provaznik & Nayara Azevedo & Stephen Cusack & Guy Schoehn & Hélène Malet, 2022. "Structural snapshots of La Crosse virus polymerase reveal the mechanisms underlying Peribunyaviridae replication and transcription," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    5. Quentin Durieux Trouilleton & Sergio Barata-García & Benoît Arragain & Juan Reguera & Hélène Malet, 2023. "Structures of active Hantaan virus polymerase uncover the mechanisms of Hantaviridae genome replication," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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