Viperin is an important host restriction factor in control of Zika virus infection
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Date
2017-06-30
Authors
van der Hoek, Kylie H
Eyre, Nicholas S
Shue, Byron
Khantisitthiporn, Onruedee
Glab-Ampi, Kittirat
Carr, Jill
Gartner, Matthew J
Jolly, Lachlan A
Thomas, Paul Q
Adikusuma, Fatwa
Journal Title
Journal ISSN
Volume Title
Publisher
Nature Publishing Group
Rights
© The Author(s) 2017
Rights Holder
The Author(s)
Abstract
Zika virus (ZIKV) infection has emerged as a global health threat and infection of pregnant women causes intrauterine growth restriction, spontaneous abortion and microcephaly in newborns. Here we show using biologically relevant cells of neural and placental origin that following ZIKV infection, there is attenuation of the cellular innate response characterised by reduced expression of IFN-β and associated interferon stimulated genes (ISGs). One such ISG is viperin that has well documented antiviral activity against a wide range of viruses. Expression of viperin in cultured cells resulted in significant impairment of ZIKV replication, while MEFs derived from CRISPR/Cas9 derived viperin−/− mice replicated ZIKV to higher titers compared to their WT counterparts. These results suggest that ZIKV can attenuate ISG expression to avoid the cellular antiviral innate response, thus allowing the virus to replicate unchecked. Moreover, we have identified that the ISG viperin has significant anti-ZIKV activity. Further understanding of how ZIKV perturbs the ISG response and the molecular mechanisms utilised by viperin to suppress ZIKV replication will aid in our understanding of ZIKV biology, pathogenesis and possible design of novel antiviral strategies.
Description
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Keywords
Zika virus, pregnancy, public health
Citation
Van der Hoek, K. H., Eyre, N. S., Shue, B., Khantisitthiporn, O., Glab-Ampi, K., Carr, J. M., ... & Jankovic-Karasoulos, T. (2017). Viperin is an important host restriction factor in control of Zika virus infection. Scientific Reports, 7.