Selective Silencing of Viral Gene E6 and E7 Expression in HPV-Positive Human Cervical Carcinoma Cells Using Small Interfering RNAs

Abstract

The newly discovered phenomenon of RNA interference (RNAi) offers the dual facility of selective viral gene silencing coupled with ease of tailoring to meet genetic variation within the viral genome. Such promise identifies RNAi as an exciting new approach to treat virus-induced diseases, including virus-induced cancers. RNAi can be induced using small interfering RNA (siRNA). Synthetic siRNA targets homologous mRNA for degradation, and this process is highly efficient. Using cervical cancer cells as a model, we demonstrate RNAi for viral oncogenes. Cervical cancer is the second most common cancer in women worldwide and is caused by human papillomavirus (HPV). Silencing of HPV E6 and E7 gene expression was achieved using siRNAs to target the respective viral mRNAs. E6 silencing induced accumulation of cellular p53 protein, transactivation of the cell cycle control p21 gene, and reduced cell growth. By contrast, E7 silencing induced apoptotic cell death. HPV-negative cells appeared to be unaffected by the antiviral siRNAs. Thus siRNA can induce selective silencing of exogenous viral genes in mammalian cells, and the process does not interfere with the recovery of cellular regulatory systems previously inhibited by viral gene expression.