Format

Send to

Choose Destination
J Virol. 2016 Oct 14;90(21):9683-9692. doi: 10.1128/JVI.01347-16. Print 2016 Nov 1.

Inhibition of Polyamine Biosynthesis Is a Broad-Spectrum Strategy against RNA Viruses.

Author information

1
Viral Populations and Pathogenesis Unit, Institut Pasteur, Paris, France.
2
Laboratory of Dendritic Cell Biology, Institut Pasteur, Paris, France Institut National de la Santé et de la Recherche Médicale, U818, Paris, France.
3
Department of Pediatrics, the Elizabeth B. Lamb Center for Pediatric Research, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
4
Viral Populations and Pathogenesis Unit, Institut Pasteur, Paris, France University Paris Diderot, Sorbonne Paris Cite, Cellule Pasteur, Paris, France.
5
Unité de Génétique Fonctionnelle des Maladies Infectieuses, Institut Pasteur, Paris, France.
6
Unité de Virologie Structurale, Institut Pasteur, Paris, France.
7
Unité de NeuroImmunologie Virale, Institut Pasteur, Paris, France.
8
Unité de Biologie des Virus Entériques, Institut Pasteur, Paris, France INSERM, Unité 994, Paris, France.
9
Unité de Recherche et d'Expertise Environnement et Risques Infectieux, Institut Pasteur, Paris, France.
10
Department of Pediatrics, the Elizabeth B. Lamb Center for Pediatric Research, Vanderbilt University Medical Center, Nashville, Tennessee, USA Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
11
Viral Populations and Pathogenesis Unit, Institut Pasteur, Paris, France marco.vignuzzi@pasteur.fr.

Abstract

RNA viruses present an extraordinary threat to human health, given their sudden and unpredictable appearance, the potential for rapid spread among the human population, and their ability to evolve resistance to antiviral therapies. The recent emergence of chikungunya virus, Zika virus, and Ebola virus highlights the struggles to contain outbreaks. A significant hurdle is the availability of antivirals to treat the infected or protect at-risk populations. While several compounds show promise in vitro and in vivo, these outbreaks underscore the need to accelerate drug discovery. The replication of several viruses has been described to rely on host polyamines, small and abundant positively charged molecules found in the cell. Here, we describe the antiviral effects of two molecules that alter polyamine levels: difluoromethylornithine (DFMO; also called eflornithine), which is a suicide inhibitor of ornithine decarboxylase 1 (ODC1), and diethylnorspermine (DENSpm), an activator of spermidine/spermine N1-acetyltransferase (SAT1). We show that reducing polyamine levels has a negative effect on diverse RNA viruses, including several viruses involved in recent outbreaks, in vitro and in vivo These findings highlight the importance of the polyamine biosynthetic pathway to viral replication, as well as its potential as a target in the development of further antivirals or currently available molecules, such as DFMO.

IMPORTANCE:

RNA viruses present a significant hazard to human health, and combatting these viruses requires the exploration of new avenues for targeting viral replication. Polyamines, small positively charged molecules within the cell, have been demonstrated to facilitate infection for a few different viruses. Our study demonstrates that diverse RNA viruses rely on the polyamine pathway for replication and highlights polyamine biosynthesis as a promising drug target.

PMID:
27535047
PMCID:
PMC5068521
DOI:
10.1128/JVI.01347-16
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for PubMed Central
Loading ...
Support Center