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

Kumar, Satyendra; Arankalle, Vidya A.

Chandipura virus (CHPV), an emerging encephalitis-causing pathogen in India belongs to family Rhabdoviridae and genus vesiculovirus. Outbreaks of CHPV have been reported from the states of Andhra Pradesh [1] , Gujarat [2] and Maharashtra [National Institute of Virology (NIV), unpublished data] with mortality varying from 55-75% in children. In an endemic area, sporadic disease has also been recorded [3] . CHPV has a negative sense RNA genome of approximately 11.0 Kb encoding 5 different proteins; nucleocapsid (N) protein, phosphoprotein (P) protein, matrix (M) protein, glycoprotein (G) protein and large (L) protein. The P protein has important functions in the virus life cycle, both in transcription and replication [4] RNA interference (RNAi) is a post-transcriptional process triggered by the introduction of double-stranded RNA (dsRNA), which is subsequently cleaved by Dicer into 21-23 nt small interfering RNAs (siRNA). The siRNAs are then unwound by RISC (RNA induced silencing complex) in the presence of ATP. The activated RISC binds and degrades target mRNA guided by the single strand of the siRNA [5] [6] [7] [8] [9] [10] [11] [12] .