Unexpected regulatory functions of cyprinid Viperin on inflammation and metabolism
2024
Chaumont, Lise | Jouneau, Luc | Huetz, François | van Muilekom, Doret R. | Peruzzi, Mathilde | Raffy, Claudine | Le Hir, Jérôme | Minke, Jules | Boudinot, Pierre | Collet, Bertrand | Virologie et Immunologie Moléculaires (VIM (UR 0892)) ; Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) | Anticorps en thérapie et pathologie - Antibodies in Therapy and Pathology ; Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité) | Laboratoires VIRBAC [Carros] | This project was funded in part by the European Union through AQUAEXCEL3.0 (Grant Agreement 871108) and AQUAFAANG (Grant Agreement 817923) and by the Research Council of Norway through the project PMCV (Project 301083). LC was a recipient of PhD funded by Virbac and the French Association for Research and Technology (ANRT) [Convention CIFRE #2020/0646] in collaboration with the Fish Infection and Immunity laboratory (INRAE, VIM, Jouy-en-Josas, France). | European Project: 871108 ,AQUAEXCEL3.0 | European Project: 817923,H2020,H2020-EU.3.2.1.1. ; H2020-EU.3.2.3.1.,AQUA-FAANG(2019)
International audience
Afficher plus [+] Moins [-]anglais. Viperin, also known as radical S-adenosyl-methionine domain containing protein 2 (RSAD2), is an interferon-inducible protein that is involved in the innate immune response against a wide array of viruses. In mammals, Viperin exerts its antiviral function through enzymatic conversion of cytidine triphosphate (CTP) into its antiviral analog ddhCTP as well as through interactions with host proteins involved in innate immune signaling and in metabolic pathways exploited by viruses during their life cycle. However, how Viperin modulates the antiviral response in fish remains largely unknown. Results: For this purpose, we developed a fathead minnow (Pimephales promelas) clonal cell line in which the unique viperin gene has been knocked out by CRISPR/Cas9 genome-editing. In order to decipher the contribution of fish Viperin to the antiviral response and its regulatory role beyond the scope of the innate immune response, we performed a comparative RNA-seq analysis of viperin−/− and wildtype cell lines upon stimulation with recombinant fathead minnow type I interferon. Conclusions: Our results revealed that Viperin does not exert positive feedback on the canonical type I IFN but acts as a negative regulator of the inflammatory response by downregulating specific pro-inflammatory genes and upregulating repressors of the NF-κB pathway. It also appeared to play a role in regulating metabolic processes, including one carbon metabolism, bone formation, extracellular matrix organization and cell adhesion.
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