Each year, up to 10,000 cases of infections with the flavivirus tick-borne encephalitis (TBE) virus that affect the central nervous system are reported in Europe and Asia. Due to the potentially severe adverse effects of post-exposure prophylaxis with TBE virus hyperimmunoglobulin, TBE can currently only be treated symptomatically. An RNA interference (RNAi) approach to inhibit TBE virus replication was therefore developed. In this study we demonstrate for the first time that small interfering RNAs (siRNAs) targeted at the TBE virus genome reduce the quantity of infectious TBE virus particles, TBE virus genome, and TBE virus protein in vitro by up to 85%. The 50% inhibitory dose (DI50) of the shRNA plasmid was only 0.05 mu g/ml. As RNAi-based therapeutics for other diseases are already being evaluated in phases II and Ill clinical trials, it is possible that RNAi could become valuable tool for controlling TBE virus infection. (C) 2011 Elsevier B.V. All rights reserved.
机构:
Umea Univ, Dept Med Biochem & Biophys, Umea, Sweden
Umea Univ, Mol Infect Med Sweden, Umea, SwedenUmea Univ, Dept Med Biochem & Biophys, Umea, Sweden
Yau, Wai-Lok
Van Nguyen-Dinh
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Umea Univ, Dept Med Biochem & Biophys, Umea, Sweden
Umea Univ, Mol Infect Med Sweden, Umea, Sweden
Philipps Univ Marburg, Inst Virol, Marburg, GermanyUmea Univ, Dept Med Biochem & Biophys, Umea, Sweden
Van Nguyen-Dinh
Larsson, Elin
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Umea Univ, Dept Integrat Med Biol, Umea, SwedenUmea Univ, Dept Med Biochem & Biophys, Umea, Sweden
Larsson, Elin
Lindqvist, Richard
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Umea Univ, Mol Infect Med Sweden, Umea, Sweden
Umea Univ, Dept Clin Microbiol, Sect Virol, Umea, SwedenUmea Univ, Dept Med Biochem & Biophys, Umea, Sweden
Lindqvist, Richard
Overby, Anna K.
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Umea Univ, Mol Infect Med Sweden, Umea, Sweden
Umea Univ, Dept Clin Microbiol, Sect Virol, Umea, SwedenUmea Univ, Dept Med Biochem & Biophys, Umea, Sweden
Overby, Anna K.
Lundmark, Richard
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Umea Univ, Dept Med Biochem & Biophys, Umea, Sweden
Umea Univ, Mol Infect Med Sweden, Umea, Sweden
Umea Univ, Dept Integrat Med Biol, Umea, SwedenUmea Univ, Dept Med Biochem & Biophys, Umea, Sweden
机构:
Univ Ljubljana, Fac Med, Inst Microbiol & Immunol, Zaloska 4, Ljubljana 1000, SloveniaUniv Ljubljana, Fac Med, Inst Microbiol & Immunol, Zaloska 4, Ljubljana 1000, Slovenia
Saksida, Ana
Jakopin, Nina
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Univ Ljubljana, Fac Med, Ljubljana, SloveniaUniv Ljubljana, Fac Med, Inst Microbiol & Immunol, Zaloska 4, Ljubljana 1000, Slovenia
Jakopin, Nina
Jelovsek, Mateja
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Univ Ljubljana, Fac Med, Ljubljana, SloveniaUniv Ljubljana, Fac Med, Inst Microbiol & Immunol, Zaloska 4, Ljubljana 1000, Slovenia
Jelovsek, Mateja
Knap, Natasa
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Univ Ljubljana, Fac Med, Ljubljana, SloveniaUniv Ljubljana, Fac Med, Inst Microbiol & Immunol, Zaloska 4, Ljubljana 1000, Slovenia
Knap, Natasa
Fajs, Luka
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Univ Ljubljana, Fac Med, Ljubljana, SloveniaUniv Ljubljana, Fac Med, Inst Microbiol & Immunol, Zaloska 4, Ljubljana 1000, Slovenia
Fajs, Luka
Lusa, Lara
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Univ Ljubljana, Fac Med, Ljubljana, SloveniaUniv Ljubljana, Fac Med, Inst Microbiol & Immunol, Zaloska 4, Ljubljana 1000, Slovenia
Lusa, Lara
Lotric-Furlan, Stanka
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Univ Med Ctr Ljubljana, Ljubljana, SloveniaUniv Ljubljana, Fac Med, Inst Microbiol & Immunol, Zaloska 4, Ljubljana 1000, Slovenia
Lotric-Furlan, Stanka
Bogovic, Petra
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Univ Med Ctr Ljubljana, Ljubljana, SloveniaUniv Ljubljana, Fac Med, Inst Microbiol & Immunol, Zaloska 4, Ljubljana 1000, Slovenia
Bogovic, Petra
Arnez, Maja
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Univ Med Ctr Ljubljana, Ljubljana, SloveniaUniv Ljubljana, Fac Med, Inst Microbiol & Immunol, Zaloska 4, Ljubljana 1000, Slovenia
Arnez, Maja
Strle, Franc
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Univ Med Ctr Ljubljana, Ljubljana, SloveniaUniv Ljubljana, Fac Med, Inst Microbiol & Immunol, Zaloska 4, Ljubljana 1000, Slovenia
Strle, Franc
Avsic-Zupanc, Tatjana
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Univ Ljubljana, Fac Med, Ljubljana, SloveniaUniv Ljubljana, Fac Med, Inst Microbiol & Immunol, Zaloska 4, Ljubljana 1000, Slovenia