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

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.
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Chaker El Kalamouni, Etienne Frumence, Sandra Bos, Jonathan Turpin, Brice Nativel, et al.. Subversion of the Heme Oxygenase-1 Antiviral Activity by Zika Virus. Viruses, MDPI, 2018, New Advances on Zika Virus Research, 11 (1), ⟨10.3390/v11010002⟩. ⟨hal-02981535⟩

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