Viruses and RNA interference in mammalian cells

diseases, including liver cirrhosis and hepatocellular carcinoma (HCC). It has a ss(+)RNA
genome, and belongs to the Flaviviridae family. Other regions of the HCV’s RNA genome,
including 5'UTR and the coding sequences of core (Yokota et al., 2003; Seo et al., 2003;
Randall et al., 2003; Kapadia et al., 2003; Wilson et al., 2003), NS3 and NS5B (Takigawa et
al., 2004) are sensitive to the action of siRNA.
Similar results with the replication inhibition of RNA viruses and others like Coxsackievirus
B3 (Yuan et al., 2005), human rhinovirus 16 (Phipps et al., 2004), poliovirus (Gitlin et al.,
2002), human parainfluenza virus-3, vesicular stomatitis virus (Barik, 2004), hepatitis delta
virus (Chang and Taylor, 2003), and rotavirus (Dector et al., 2002) with the help of artificial
siRNAs and mammalian cell enzymes serve as an evidence, that the mammalian cellular
RNAi machinery can inhibit virus replication. These findings open a wide range of
enormous therapeutical potential of RNAi.
In summary, these in vitro studies is the first step to demonstrate that siRNA technology is a
very promising approach to antiviral gene therapy. RNAi based therapies for some viruses
have already reached clinical trials. However, there are still many concerns of the
widespread application of RNAi in treatment of human diseases (Kim and Rossi, 2007).
5. Suppression of cellular anti-viral RNAi by viruses
During infection dsRNA molecules are produced, which can trigger RNAi. To counteract
this and avoid recognition by the RNAi machinery of the host, viruses have evolved special
strategies (Berkhout and Haasnoot, 2006). Many mammalian viruses can encode proteins or
RNA molecules that suppress existing RNAi pathways or trigger the silencing of specific
host genes (Chen et al., 2005). Like the plant viruses, which encode proteins that interfere
with one or more aspects of Dicer action and/or siRNA targeting (Vance and Vaucheret,
2001; Voinnet et al., 1999), mammalian viruses also encode such molecules. The fact, that
animal RNA viruses have RNA silencing suppressors (RSSs) might serve as evidence that
RNAi acts as an antiviral defense also in mammalian cells. These suppressors block induced
RNAi against reporter gene constructs. However, functional significance of RNAi for viral
pathogenesis must be investigated (van Rij and Andino, 2006). Recently, several human
pathogenic viruses have been shown to encode RSSs, suggesting that RNAi serves as an
innate defense response in mammals (Li and Ding, 2001).
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