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A specific domain within the 3′ untranslated region of Usutu virus confers resistance to the exonuclease ISG20

Author

Listed:
  • Jim Zoladek

    (CNRS UMR 9004)

  • Priscila El Kazzi

    (CNRS UMR 7257)

  • Vincent Caval

    (Université Paris Cité)

  • Valérie Vivet-Boudou

    (UPR 9002)

  • Marion Cannac

    (CNRS UMR 9004)

  • Emma L. Davies

    (University of Glasgow)

  • Soléna Rossi

    (CNRS UMR 9004)

  • Inès Bribes

    (CNRS UMR 9004)

  • Lucile Rouilly

    (CNRS UMR 7257)

  • Yannick Simonin

    (Université de Montpellier)

  • Nolwenn Jouvenet

    (Université Paris Cité)

  • Etienne Decroly

    (CNRS UMR 7257)

  • Jean-Christophe Paillart

    (UPR 9002)

  • Sam J. Wilson

    (University of Glasgow
    University of Cambridge)

  • Sébastien Nisole

    (CNRS UMR 9004)

Abstract

Usutu virus (USUV) and West Nile virus (WNV) are two closely related emerging mosquito-borne flaviviruses. Their natural hosts are wild birds, but they can also cause severe neurological disorders in humans. Both viruses are efficiently suppressed by type I interferon (IFN), which interferes with viral replication, dissemination, pathogenesis and transmission. Here, we show that the replication of USUV and WNV are inhibited through a common set of IFN–induced genes (ISGs), with the notable exception of ISG20, which USUV is resistant to. Strikingly, USUV was the only virus among all the other tested mosquito-borne flaviviruses that demonstrated resistance to the 3′–5′ exonuclease activity of ISG20. Our findings highlight that the intrinsic resistance of the USUV genome, irrespective of the presence of cellular or viral proteins or protective post-transcriptional modifications, relies on a unique sequence present in its 3′ untranslated region. Importantly, this genomic region alone can confer ISG20 resistance to a susceptible flavivirus, without compromising its infectivity, suggesting that it could be acquired by other flaviviruses. This study provides new insights into the strategy employed by emerging flaviviruses to overcome host defense mechanisms.

Suggested Citation

  • Jim Zoladek & Priscila El Kazzi & Vincent Caval & Valérie Vivet-Boudou & Marion Cannac & Emma L. Davies & Soléna Rossi & Inès Bribes & Lucile Rouilly & Yannick Simonin & Nolwenn Jouvenet & Etienne Dec, 2024. "A specific domain within the 3′ untranslated region of Usutu virus confers resistance to the exonuclease ISG20," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-52870-w
    DOI: 10.1038/s41467-024-52870-w
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    References listed on IDEAS

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    1. John W. Schoggins & Sam J. Wilson & Maryline Panis & Mary Y. Murphy & Christopher T. Jones & Paul Bieniasz & Charles M. Rice, 2011. "A diverse range of gene products are effectors of the type I interferon antiviral response," Nature, Nature, vol. 472(7344), pages 481-485, April.
    2. Andrea MacFadden & Zoe O’Donoghue & Patricia A. G. C. Silva & Erich G. Chapman & René C. Olsthoorn & Mark G. Sterken & Gorben P. Pijlman & Peter J. Bredenbeek & Jeffrey S. Kieft, 2018. "Mechanism and structural diversity of exoribonuclease-resistant RNA structures in flaviviral RNAs," Nature Communications, Nature, vol. 9(1), pages 1-11, December.
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