A specific domain within the 3′ untranslated region of Usutu virus confers resistance to the exonuclease ISG20
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.
Authors
- Sam J. Wilson (ORCID: https://orcid.org/0000-0002-6065-0895)
- Inès Bribes
- Vincent Caval (ORCID: https://orcid.org/0000-0002-5458-6081)
- Priscila El Kazzi
- Valérie Vivet‐Boudou (ORCID: https://orcid.org/0000-0001-8702-1047)
- Nolwenn Jouvenet (ORCID: https://orcid.org/0000-0001-6103-6048)
- Marion Cannac (ORCID: https://orcid.org/0000-0001-8907-7650)
- Jean‐Christophe Paillart (ORCID: https://orcid.org/0000-0003-1647-8917)
- Sébastien Nisole (ORCID: https://orcid.org/0000-0001-9793-419X)
- Yannick Simonin (ORCID: https://orcid.org/0000-0002-3475-1369)
- Étienne Decroly (ORCID: https://orcid.org/0000-0002-6046-024X)
- Jim Zoladek (ORCID: https://orcid.org/0000-0003-0715-251X)
- Emma L. Davies (ORCID: https://orcid.org/0000-0002-8416-9203)
- Lucile Rouilly
- Soléna Rossi
Institutions
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Institut Pasteur (FR)
- Université Paris Cité (FR)
- University of Cambridge (GB)
- Architecture et Réactivité de l'arN (FR)
- Établissement Français du Sang (FR)
- Institut de Recherche en Infectiologie de Montpellier (FR)
- MRC University of Glasgow Centre for Virus Research (GB)
- Architecture et Fonction des Macromolécules Biologiques (FR)
- Université de Strasbourg (FR)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-10-02
- DOI
- https://doi.org/10.1038/s41467-024-52870-w
- Citations
- 14
- Primary Topic
- Mosquito-borne diseases and control
- Type
- article
- Field-Weighted Citation Impact
- 7.60
Funders
- European Commission
- Agence Nationale de la Recherche
- Fondation pour la Recherche Médicale
- Ministère de l'Education Nationale, de l'Enseignement Superieur et de la Recherche
- Medical Research Council
- Medical Research Foundation