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Viruses 2019, 11(1), 2; https://doi.org/10.3390/v11010002

Subversion of the Heme Oxygenase-1 Antiviral Activity by Zika Virus

1
Université de La Réunion, INSERM UMR 1187, CNRS 9192, IRD 249 UMR PIMIT, Processus Infectieux en Milieu Insulaire Tropical, Plateforme CYROI, 2, rue Maxime Rivière, F-97490 Sainte-Clotilde, France
2
Université de la Réunion, Inserm, UMR 1188 Diabète Athérothrombose Thérapies Réunion Océan Indien (DéTROI), F-97490 Sainte-Clotilde, France
3
CHU de La Réunion, Saint-Denis de La Réunion, F-97400 Bellepierre, France
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Received: 15 October 2018 / Revised: 13 December 2018 / Accepted: 18 December 2018 / Published: 20 December 2018
(This article belongs to the Special Issue New Advances on Zika Virus Research)
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Abstract

Heme oxygenase-1 (HO-1), a rate-limiting enzyme involved in the degradation of heme, is induced in response to a wide range of stress conditions. HO-1 exerts antiviral activity against a broad range of viruses, including the Hepatitis C virus, the human immunodeficiency virus, and the dengue virus by inhibiting viral growth. It has been reported that HO-1 displays antiviral activity against the Zika virus (ZIKV) but the mechanisms of viral inhibition remain largely unknown. Using a ZIKV RNA replicon with the Green Fluorescent Protein (GFP) as a reporter protein, we were able to show that HO-1 expression resulted in the inhibition of viral RNA replication. Conversely, we observed a decrease in HO-1 expression in cells replicating the ZIKV RNA replicon. The study of human cells infected with ZIKV showed that the HO-1 expression level was significantly lower once viral replication was established, thereby limiting the antiviral effect of HO-1. Our work highlights the capacity of ZIKV to thwart the anti-replicative activity of HO-1 in human cells. Therefore, the modulation of HO-1 as a novel therapeutic strategy against ZIKV infection may display limited effect. View Full-Text
Keywords: antiviral; heme-oxygenase 1; Zika virus; viral replication antiviral; heme-oxygenase 1; Zika virus; viral replication
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El Kalamouni, C.; Frumence, E.; Bos, S.; Turpin, J.; Nativel, B.; Harrabi, W.; Wilkinson, D.A.; Meilhac, O.; Gadea, G.; Desprès, P.; Krejbich-Trotot, P.; Viranaïcken, W. Subversion of the Heme Oxygenase-1 Antiviral Activity by Zika Virus. Viruses 2019, 11, 2.

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