title: Interferon-Induced Spermidine-Spermine Acetyltransferase and Polyamine Depletion Restrict Zika and Chikungunya Viruses.
abstract: Polyamines are small, positively charged molecules derived from ornithine and synthesized through an intricately regulated enzymatic pathway. Within cells, they are abundant and play several roles in diverse processes. We find that polyamines are required for the life cycle of the RNA viruses chikungunya virus (CHIKV) and Zika virus (ZIKV). Depletion of spermidine and spermine via type I interferon signaling-mediated induction of spermidine/spermine N1-acetyltransferase (SAT1), a key catabolic enzyme in the polyamine pathway, restricts CHIKV and ZIKV replication. Polyamine depletion restricts these viruses in vitro and in vivo, due to impairment of viral translation and RNA replication. The restriction is released by exogenous replenishment of polyamines, further supporting a role for these molecules in virus replication. Thus, SAT1 and, more broadly, polyamine depletion restrict viral replication and suggest promising avenues for antiviral therapies.
authors.affiliation: Viral Populations and Pathogenesis Unit, Institut Pasteur, CNRS UMR 3569, 25-28 rue du Dr. Roux, 75724 Paris Cedex 15, France.
authors.forename: Bryan C
authors.initials: BC
authors.lastname: Mounce
authors.affiliation: Viral Populations and Pathogenesis Unit, Institut Pasteur, CNRS UMR 3569, 25-28 rue du Dr. Roux, 75724 Paris Cedex 15, France; University of Paris Diderot, Sorbonne Paris Cité, Cellule Pasteur, 75013 Paris, France.
authors.forename: Enzo Z
authors.initials: EZ
authors.lastname: Poirier
authors.affiliation: Virologie et Immunologie Moléculaire, INRA, Domaine de Vilvert, 78352 Jouy-en-Josas, France; Macrophages et Développement de l'Immunité, Institut Pasteur, 25-28 rue du Dr. Roux, 75724 Paris Cedex 15, France; CNRS URA2578, 75724 Paris Cedex 15, France.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Passoni
authors.affiliation: Unité de Génétique Fonctionnelle des Maladies Infectieuses, Institut Pasteur, 25-28 rue du Dr. Roux, 75724 Paris Cedex 15, France.
authors.forename: Etienne
authors.initials: E
authors.lastname: Simon-Loriere
authors.affiliation: Viral Populations and Pathogenesis Unit, Institut Pasteur, CNRS UMR 3569, 25-28 rue du Dr. Roux, 75724 Paris Cedex 15, France.
authors.forename: Teresa
authors.initials: T
authors.lastname: Cesaro
authors.affiliation: Unité de Génétique Fonctionnelle des Maladies Infectieuses, Institut Pasteur, 25-28 rue du Dr. Roux, 75724 Paris Cedex 15, France.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Prot
authors.affiliation: Viral Populations and Pathogenesis Unit, Institut Pasteur, CNRS UMR 3569, 25-28 rue du Dr. Roux, 75724 Paris Cedex 15, France.
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Stapleford
authors.affiliation: Viral Populations and Pathogenesis Unit, Institut Pasteur, CNRS UMR 3569, 25-28 rue du Dr. Roux, 75724 Paris Cedex 15, France.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Moratorio
authors.affiliation: Unité de Génétique Fonctionnelle des Maladies Infectieuses, Institut Pasteur, 25-28 rue du Dr. Roux, 75724 Paris Cedex 15, France.
authors.forename: Anavaj
authors.initials: A
authors.lastname: Sakuntabhai
authors.affiliation: Macrophages et Développement de l'Immunité, Institut Pasteur, 25-28 rue du Dr. Roux, 75724 Paris Cedex 15, France; CNRS URA2578, 75724 Paris Cedex 15, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Levraud
authors.affiliation: Viral Populations and Pathogenesis Unit, Institut Pasteur, CNRS UMR 3569, 25-28 rue du Dr. Roux, 75724 Paris Cedex 15, France. Electronic address: marco.vignuzzi@pasteur.fr.
authors.forename: Marco
authors.initials: M
authors.lastname: Vignuzzi
mesh_terms: D000123:Acetyltransferases / Q000378:metabolism*; D002646:Chikungunya virus / Q000502:physiology*; D011073:Polyamines / Q000378:metabolism*; D013095:Spermidine / Q000378:metabolism*; D013096:Spermine / Q000378:metabolism*; D014779:Virus Replication; D000071244:Zika Virus / Q000502:physiology*; D000099228:Diamine N-Acetyltransferase
chemical_list: D000123:Acetyltransferases; D011073:Polyamines; D013095:Spermidine; D013096:Spermine; D000099228:Diamine N-Acetyltransferase