Inhibition of DNA Viruses by RNAi

HSV-1 is a large DNA virus that infects epithelial and neuronal cells. Bhuyan and co-workers used siRNAs against glycoprotein E (gE) to inhibit HSV-1 replication. The gE is important for cell-to-cell spread and evasion from complement and antibody responses, and silencing the expression of gE resulted in a fourfold inhibition of HSV-1 replication (Bhuyan et al. 2004). An 11- to 16-fold inhibition of the gamma herpesvirus EBV was obtained with shRNA against the essential viral gene Zta (Chang et al. 2004). Zta is involved in the reactivation of EBV and important for expression of lytic genes and viral DNA replication. In addition to targeting EBV replication, one report describes inhibition of an EBV oncogene to inhibit the pathogenic effects of EBV infection (Li et al. 2004a). EBV is associated with the development of highly metastatic nasopharyngeal carcinoma (NPC). Important in the development of NPC is the viral latent membrane protein-1 (LMP-1), which is involved in cell transformation and tumour metastasis. Suppression of LMP-1 expression by RNAi resulted in altered cell motility, surface adhesion and transmembrane invasion ability, suggesting that RNAi can be used to inhibit the metastatic potential of the EBV-positive carcinoma cells.

Two studies have used RNAi to inhibit the small DNA virus human poly-omavirus JCV (Orba et al. 2004; Radhakrishnan et al. 2004). JCV can cause progressive multifocal leukoencephalopathy (PML) in patients with impaired immune systems. As such, PML has become a major neurologic problem among patients with AIDS. In both studies, synthetic siRNAs were used to target the VP1, Agno and T-Ag genes, resulting in 10- to 24-fold inhibition of virus replication in vitro.

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