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Volume 102, Issue 10

Viperin is anti-viral but is dispensable for restricting dengue virus replication or induction of innate and inflammatory responses Open Access

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 and in a mouse 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 , for DENV infection a lack of viperin does not affect systemic or brain susceptibility to DENV or induction of innate and inflammatory responses.

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  • Accepted:
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Keyword(s): dengue virus , inflammatory response , interferon response , neurovirulence and viperin
© 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.
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2021-10-19
2024-04-19
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Viperin is anti-viral in vitro but is dispensable for restricting dengue virus replication or induction of innate and inflammatory responses in vivo
J. Gen. Virol. 102, 001669 (2021); https://doi.org/10.1099/jgv.0.001669
/content/journal/jgv/10.1099/jgv.0.001669
/content/journal/jgv/10.1099/jgv.0.001669
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