Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/134318
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Type: | Journal article |
Title: | Viperin is anti-viral in vitro but is dispensable for restricting dengue virus replication or induction of innate and inflammatory responses in vivo |
Author: | Al Shujairi, W.-H. Kris, L.P. Van Der Hoek, K. Cowell, E. Bracho-Granado, G. Woodgate, T. Beard, M.R. Carr, J.M. |
Citation: | Journal of General Virology, 2021; 102(10):001669-1-001669-14 |
Publisher: | Microbiology Society |
Issue Date: | 2021 |
ISSN: | 0022-1317 1465-2099 |
Statement of Responsibility: | Wisam-Hamzah Al Shujairi, Luke P. Kris, Kylie van der Hoek, Evangeline Cowell, Gustavo Bracho-Granado, Tahlia Woodgate, Michael R. Beard and Jillian M. Carr |
Abstract: | Viperin has antiviral function against many viruses, including dengue virus (DENV), when studied in cells in culture. Here, the antiviral actions of viperin were defined both in vitro and in a mouse in vivo model of DENV infection. Murine embryonic fibroblasts (MEFs) derived from mice lacking viperin (vip(-/-)) showed enhanced DENV infection, accompanied by increased IFN-β and induction of ISGs; IFIT1 and CXCL-10 but not IRF7, when compared to wild-type (WT) MEFs. In contrast, subcutaneous challenge of immunocompetent WT and vip(-/-) mice with DENV did not result in enhanced infection. Intracranial infection with DENV resulted in body weight loss and neurological disease with a moderate increase in mortality in vip(-/)- compared with WT mice, although this was not accompanied by altered brain morphology, immune cell infiltration or DENV RNA level in the brain. Similarly, DENV induction of IFN-β, IFIT1, CXCL-10, IRF7 and TNF-α was not significantly different in WT and vip(-/-) mouse brain, although there was a modest but significant increase in DENV induction of IL-6 and IfI27la in the absence of viperin. NanoString nCounter analysis confirmed no significant difference in induction of a panel of inflammatory genes in WT compared to vip(-/-) DENV-infected mouse brains. Further, polyI:C stimulation of bone marrow-derived macrophages (BMDMs) induced TNF-α, IFN-β, IL-6 and Nos-2, but responses were not different in BMDMs generated from WT or vip(-/-) mice. Thus, while there is significant evidence of anti-DENV actions of viperin in some cell types in vitro, for DENV infection in vivo a lack of viperin does not affect systemic or brain susceptibility to DENV or induction of innate and inflammatory responses. |
Keywords: | Dengue virus; interferon response; inflammatory response; neurovirulence; viperin |
Rights: | © 2021 The Authors. This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution. |
DOI: | 10.1099/jgv.0.001669 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/1145613 |
Published version: | http://dx.doi.org/10.1099/jgv.0.001669 |
Appears in Collections: | Medicine publications |
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File | Description | Size | Format | |
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hdl_134318.pdf | Published version | 2.8 MB | Adobe PDF | View/Open |
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