Inhibition of human cytomegalovirus DNA replication by small interfering RNAs targeted to UL49.

Human cytomegalovirus (HCMV) is a ubiquitous virus. Although the infection in healthy children and adults is usually asymptomatic, in immunocompromised individuals and newborns it is a significant cause of morbidity and mortality. UL49, an essential gene of HCMV, is highly conserved among various HCMV strains. The expression of UL49 is correlated with the production of virions. When UL49 is inhibited in the HCMV, the production of virions is reduced severely. In this study, RNA interference was applied to further investigate the roles of UL49 in viral replication. Two effective small interfering RNAs against UL49 were selected. Silencing of UL49 in HCMV-infected human foreskin fibroblast cells reduced the transcription levels of early and late genes, but not immediate-early ones. In addition, the viral DNA content was significantly reduced. This is the first time to uncover the role of UL49 in viral DNA synthesis, which indicates that UL49 might play an important role in this period. So the down-regulation of UL49 mRNA using RNAi might be a potential clinical therapy against the virus.