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

Date Published: January 7, 2010

Publisher: Public Library of Science

Author(s): Satyendra Kumar, Vidya A. Arankalle, Bradley S. Schneider.

Abstract: In parts of India, Chandipura Virus (CHPV) has emerged as an encephalitis causing pathogen in both epidemic and sporadic forms. This pediatric disease follows rapid course leading to 55–75% mortality. In the absence of specific treatment, effectiveness of RNA interference (RNAi) was evaluated.

Partial Text: 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been reported from the states of Andhra Pradesh [1], Gujarat [2] and Maharashtra [National Institute of Virology (NIV), unpublished data] with mortality varying from 55–75% in children.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]

Following the recognition of emergence of CHPV as an emerging pathogen causing rapid and high mortality in children in India, being the national institute and considering restricted spread of the virus, we undertook two approaches as probable strategies to combat the infection, development of a prophylactic vaccine [28] and siRNA administration as a probable therapeutic agent (present study). We were able to identify a potent siRNA that could protect mice from the lethal encephalitis even when the virus was directly introduced in the target organ, the brain.



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