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262 : Viperin vs. tick-borne encephalitis virus: Mechanisms of a potent antiviral protein
Journal article   Peer reviewed

262 : Viperin vs. tick-borne encephalitis virus: Mechanisms of a potent antiviral protein

Arunkumar S. Upadhyay, Kirstin Vonderstein, Andreas Pichlmair, Oliver Stehling, Ju-Tao Guo, Roland Lill, Friedemann Weber and Anna K. Överby
Cytokine (Philadelphia, Pa.), v 63(3), pp 305-305
Sep 2013
DOI: https://doi.org/10.1016/j.cyto.2013.06.265
Featured in Collection :   UN Sustainable Development Goals @ Drexel

Abstract

Tick-borne encephalitis virus (TBEV; family Flaviviridae), a positive sense, single-stranded RNA virus, is the medical most important arbovirus in Europe and Russia. TBEV has a significant impact on public health as it causes ∼10,000 annual cases of encephalitis and meningitis, and no antiviral treatment is available. We are investigating TBEVs interactions with the interferon (IFN) system. Therefore, three different Western TBEV strains were tested for their sensitivity to IFNa pre-treatment, measuring virus replication in cells and virus load in the supernatant. TBEV turned out to be very sensitive to IFN, as viral RNA and titres were reduced by up to three logs after treatment with 100 units IFN alpha. To identify the cellular protein mediating the anti TBEV effect of IFN alpha, a screen of inducible cell lines expressing different ISGs was performed. This screen identified viperin as a very strong inhibitor of virus replication. Viperin is an interferon-induced protein with a broad antiviral activity. However, the mechanism of action is not clear. Since TBEV is extremely viperin sensitive it is a perfect model virus for investigating the antiviral mechanism of viperin. This evolutionary conserved protein contains a radical S-adenosyl-L-methionine (SAM) domain with a [4Fe–4S] cluster. We have shown that wt viperin requires ER localization for full antiviral activity, interacts with the cytosolic Fe/S protein assembly factor CIAO1, and incorporates 55Fe. We have also set up a number of assays to determine which step of the virus lifecycle that viperin is targeting and screened a set of mutants to determine which domains are responsible for the antiviral activity of viperin.

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Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Biochemistry & Molecular Biology
Cell Biology
Immunology
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