Vero cells as a model to study the effects of adenoviral gene delivery vectors on the RNAi system in context of viral infection

Abstract

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-α and IFN-β 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. © 2009 S. Karger AG, Basel.