MITD1 is a brain-specific interferon-inducible factor that inhibits flavivirus replication

Zoladek Jim, Cannac Marion, Seite Maël, Davies Emma, Quellec Jordan, Barthelemy Jonathan, Gorna Kamila, Desgraupes Sophie, Bribes Ines, Salinas Sara, Coulpier Muriel, Arhel Nathalie J., Palmarini Massimo, Simonin Yannick, Wilson Sam J., Nisole Sébastien. 2025. MITD1 is a brain-specific interferon-inducible factor that inhibits flavivirus replication. Proceedings of the National Academy of Sciences of the United States of America, 122 (12), 12 p.

Liste HCERES des revues (en SHS) : oui

Thème(s) HCERES des revues (en SHS) : Economie-gestion; Psychologie-éthologie-ergonomie

Résumé : West Nile virus (WNV) and Usutu virus (USUV) are closely related mosquito-borne neurotropic flaviviruses that share common transmission cycle and can infect humans. However, while human infections by WNV are widespread, infections by USUV are comparatively less frequent, less severe, and currently limited to Africa and Europe. To identify human host factors that contribute to the pathogenic signatures of these two flaviviruses, we carried out an arrayed expression screen of over 1,300 interferon-stimulated genes (ISGs). Several ISGs known to target flaviviruses, including IFI6, SHFL, and RTP4 were among the strongest hits. Interestingly, we also found MITD1, an ISG with no previously reported antiviral activity, among the strongest hits. We demonstrated that the antiviral activity of MITD1 was not limited to USUV and WNV, since it also inhibited Zika and dengue virus replication. We found MITD1 to interfere with viral RNA replication by sequestering specific endosomal sorting complexes required for transport-III (ESCRT-III) proteins involved in the formation of viral replication factories. MITD1 expression was not increased by type I interferon (IFN-I) in most human cells and mouse tissues that we examined, although WNV and USUV replication was strongly inhibited by IFN-I. Strikingly, MITD1 was induced in the brain of USUV-infected mice and importantly, in human monocyte-derived microglia. Using human microglial-like cells, we confirmed that MITD1 is an essential mediator of the anti-flavivirus activity of IFN-I in these cells. We conclude that MITD1 plays a key role in the cellular defenses against neurotropic flaviviruses.

Mots-clés Agrovoc : flavivirus, genre humain, virus Zika, santé publique, transmission des maladies, maladie de l'homme

Mots-clés géographiques Agrovoc : France

Mots-clés libres : Flavivirus, Interferon-stimulated gene, Innate immune response, Microglial cells

Agences de financement hors UE : Agence Nationale de la Recherche, Medical Research Council

Projets sur financement : (FRA) Caractéristiques cliniques et mécanismes moléculaires de la neuroinflammation et des dommages neurovasculaires induits par les arbovirus

Auteurs et affiliations

• Zoladek Jim, CNRS (FRA)
• Cannac Marion, CNRS (FRA)
• Seite Maël, CNRS (FRA)
• Davies Emma, University of Glasgow (GBR)
• Quellec Jordan, INSERM (FRA)
• Barthelemy Jonathan, INSERM (FRA)
• Gorna Kamila, ANSES (FRA)
• Desgraupes Sophie, CNRS (FRA)
• Bribes Ines, CNRS (FRA)
• Salinas Sara, Université de Montpellier (FRA)
• Coulpier Muriel, INRAE (FRA)
• Arhel Nathalie J., CNRS (FRA)
• Palmarini Massimo, University of Glasgow (GBR)
• Simonin Yannick, CIRAD-BIOS-UMR ASTRE (FRA)
• Wilson Sam J., University of Glasgow (GBR)
• Nisole Sébastien, CNRS (FRA) - auteur correspondant

Source : Cirad-Agritrop (https://agritrop.cirad.fr/613637/)

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