B. Canard’s team guest: Jim Zoladek, IRIM, Montpellier – “The distinctive resistance of Usutu virus among flaviviruses unveils new insights into the ISG20 restrictome”

Abstract

Usutu virus (USUV) and West Nile virus (WNV) are two closely related emerging mosquito-borne flaviviruses causing severe neurological disorders in wild birds and humans. Both viruses are efficiently suppressed by type I interferon (IFN) and 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 flaviriruses 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 stem-loop structure 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. 

Mini CV

• (2012-2016) Licence (dont PACES) de sciences de la vie
• (2016-2018) Master Infectiologie, mention Virologie fondamentale (cours Institut Pasteur)
• (2018-2021) Doctorat infectiologie (https://www.theses.fr/2021UNIP7317) avec Philippe AFONSO, Institut Pasteur
  Infection des cellules endothéliales humaines par le virus Zika : rôle des claudines dans l’infection et comme modèles de développement de molécules thérapeutiques
• (2022-présent) Postdoc avec Sebastien Nisole, IRIM

References 

• Zoladek J & Nisole S (2023). Mosquito-borne flaviviruses and type I interferon: Catch me if you can!. Frontiers in Microbiology.
• Zoladek J, Burlaud-Gaillard J, Chazal M, Desgraupes S, Jeannin P, Gessain A, Pardigon N, Hubert M, Roingeard P, Jouvenet N & Afonso PV (2022). Human claudin-derived peptides block the membrane fusion process of Zika virus and are broad flavivirus inhibitors. Microbiology Spectrum.
• Zoladek J, Legros V, Jeannin P, Pardigon N, Ceccaldi PE, Gessain A & Afonso PV (2021). Zika virus requires the expression of Claudin-7 for optimal replication in human endothelial cells. Frontiers in Microbiology.