Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
J Innate Immun. 2009;1(4):389-94. doi: 10.1159/000191408. Epub 2009 Jan 8.
Technology based on RNA interference (RNAi) is a promising source for new antiviral therapies. Although the application of RNAi has been studied extensively, significant problems with using RNAi remain. Very few studies have specifically assessed model systems for testing the effects of viruses or gene delivery vectors on the RNAi system. Since viruses have developed efficient strategies to circumvent the interferon (IFN) response, an IFN-deficient model system should be considered. Here we show that in Vero cells, which lack IFN-alpha and IFN-beta genes, knockdown of Dicer, a key RNAi component, led to accelerated death of cells infected with other evolutionary distinct viruses: influenza A virus, vesicular stomatitis virus and poliovirus. We also demonstrate that transduction of Vero cells with adenoviral vector with subsequent infection with influenza A virus also resulted in increased mortality of infected cells. These effects were much weaker in IFN-producing A549 and Hela cell lines. Thus, the Vero cell line could serve as an interesting model for studying the effects of gene delivery vectors on the RNAi system in the context of virus-related disorders.
基于 RNA 干扰 (RNAi) 的技术是一种有前途的新型抗病毒疗法来源。尽管 RNAi 的应用已经得到了广泛的研究，但在使用 RNAi 方面仍存在一些重大问题。很少有研究专门评估模型系统，以测试病毒或基因传递载体对 RNAi 系统的影响。由于病毒已经开发出有效的策略来规避干扰素 (IFN) 反应，因此应该考虑使用 IFN 缺陷型模型系统。在这里，我们展示了在缺乏 IFN-α和 IFN-β 基因的 Vero 细胞中，RNAi 的关键成分 Dicer 的敲低导致感染其他进化上不同的病毒（流感 A 病毒、水疱性口炎病毒和脊髓灰质炎病毒）的细胞加速死亡。我们还证明，用腺病毒载体转导 Vero 细胞，随后感染流感 A 病毒也会导致感染细胞的死亡率增加。在产生 IFN 的 A549 和 Hela 细胞系中，这些影响要弱得多。因此，Vero 细胞系可以作为研究基因传递载体在与病毒相关的疾病背景下对 RNAi 系统影响的有趣模型。
