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Cell Host Microbe. 2016 Aug 10;20(2):167-77. doi: 10.1016/j.chom.2016.06.011. Epub 2016 Jul 14.

Interferon-Induced Spermidine-Spermine Acetyltransferase and Polyamine Depletion Restrict Zika and Chikungunya Viruses.

Author information

1
Viral Populations and Pathogenesis Unit, Institut Pasteur, CNRS UMR 3569, 25-28 rue du Dr. Roux, 75724 Paris Cedex 15, France.
2
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.
3
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.
4
Unité de Génétique Fonctionnelle des Maladies Infectieuses, Institut Pasteur, 25-28 rue du Dr. Roux, 75724 Paris Cedex 15, France.
5
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.
6
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.

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.

PMID:
27427208
DOI:
10.1016/j.chom.2016.06.011
[Indexed for MEDLINE]
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