Intracranial Administration of P Gene siRNA Protects Mice from Lethal Chandipura Virus Encephalitis

Kumar, Satyendra; Arankalle, Vidya A.

Considering several advantages offered by shRNA such as requirement for low doses, long-term downregulation of the target gene and an economic alternative to the siRNA, we also tried the shRNA format. Though efficient silencing was observed at 12hr, the efficacy was lost at 24hr (Fig 6b) . This could possibly be because of apoptosis and subsequent inhibition of host transcription induced by M protein for both CHPV [34] and VSV [35] infections. Similar to our findings, abrogation of DNA based RNAi was found in apoptotic cells due to caspace-3 mediated inactivation of Dicer-1 without affecting RISC dependent part of RNAi [36] . Therefore, siRNA seems to be a better approach for regulating CHPV replication especially because it is an acute infection with rapid course and long-term treatment is not needed. However, in a recent study, efficacy of shRNA was effectively shown for the treatment of JEV encephalitis in mice by using lentiviral vector. 100% survival was recorded when mice were injected IC with pseudotyped RV-G lentiviral vector expressing shRNA specific for JEV and challenged half an hour later with 4 LD 50 of JEV at the same site [20] .