| Autor: |
Al Shujairi WH; College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia.; Department of Clinical Laboratory Sciences, College of Pharmacy, University of Babylon, 51001 Hilla, Iraq., Kris LP; College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia., van der Hoek K; School of Biological Sciences, Research Centre for Infectious Diseases, The University of Adelaide, Adelaide, SA 5005, Australia., Cowell E; College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia., Bracho-Granado G; College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia., Woodgate T; College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia., Beard MR; School of Biological Sciences, Research Centre for Infectious Diseases, The University of Adelaide, Adelaide, SA 5005, Australia., Carr JM; College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia. |
| Abstrakt: |
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. |
