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Journal article
Viperin is an iron-sulfur protein that inhibits genome synthesis of tick-borne encephalitis virus via radical SAM domain activity
Cellular microbiology, v 16(6), pp 834-848
01 Jun 2014
PMID: 24245804
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Viperin is an interferon-induced protein with a broad antiviral activity. This evolutionary conserved protein contains a radical S-adenosyl-l-methionine (SAM) domain which has been shown in vitro to hold a [4Fe-4S] cluster. We identified tick-borne encephalitis virus (TBEV) as a novel target for which human viperin inhibits productionof the viral genome RNA. Wt viperin was found to require ER localization for full antiviral activity and to interact with the cytosolic Fe/S protein assembly factor CIAO1. Radiolabelling in vivo revealed incorporation of Fe-55, indicative for the presence of an Fe-S cluster. Mutation of the cysteine residues ligating the Fe-S cluster in the central radical SAM domain entirely abolished both antiviral activity and incorporation of Fe-55. Mutants lacking the extreme C-terminal W361 did not interact with CIAO1, were not matured, and were antivirally inactive. Moreover, intracellular removal of SAM by ectopic expression of the bacteriophage T3 SAMase abolished antiviral activity. Collectively, our data suggest that viperin requires CIAO1 for [4Fe-4S] cluster assembly, and acts through an enzymatic, Fe-S cluster- and SAM-dependent mechanism to inhibit viral RNA synthesis.
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- Title
- Viperin is an iron-sulfur protein that inhibits genome synthesis of tick-borne encephalitis virus via radical SAM domain activity
- Creators
- Arunkumar S. Upadhyay - Umeå UniversityKirstin Vonderstein - Umeå UniversityAndreas Pichlmair - Pichlmair, Andreas / Innate Immunity, Max Planck Institute of Biochemistry, Max Planck SocietyOliver Stehling - Philipp University of MarburgKeiryn L. Bennett - CeMM Research Center for Molecular MedicineGerhard Dobler - Bundeswehr Institute of MicrobiologyJu-Tao Guo - Drexel UniversityGiulio Superti-Furga - CeMM Research Center for Molecular MedicineRoland Lill - Philipp University of MarburgAnna K. Oeverby - Umea Univ, Dept Clin Microbiol, SE-90185 Umea, SwedenFriedemann Weber - Department of Virology; University Freiburg; D-79008 Freiburg Germany
- Publication Details
- Cellular microbiology, v 16(6), pp 834-848
- Publisher
- Wiley
- Number of pages
- 15
- Grant note
- laboratory for molecular infection medicine Sweden (MIMS) von Behring-Rontgen Stiftung Max-Planck Gesellschaft; Max Planck Society LOEWE programme of state Hessen SFB 593; GRK 1216 / DFG; German Research Foundation (DFG); European Commission JCK-1120 / Kempe Foundation SFB 593 / Deutsche Forschungsgemeinschaft (DFG); German Research Foundation (DFG) 2011-2795 / Swedish research council; Swedish Research Council; European Commission 01 KI 0711 / Bundesministerium fur Bildung und Forschung (BMBF); Federal Ministry of Education & Research (BMBF) ICA 10-0059 / Swedish foundation for strategic research; Swedish Foundation for Strategic Research
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:000335930200004
- Scopus ID
- 2-s2.0-84900537886
- Other Identifier
- 991019168443104721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Cell Biology
- Microbiology