Open AccessA Single siRNA Suppresses Fatal Encephalitis Induced by Two Different Flaviviruses
Author(s) -
Priti Kumar,
Sang Kyung Lee,
Premlata Shankar,
N. Manjunath
Publication year - 2006
Publication title -
plos medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.847
H-Index - 228
eISSN - 1549-1676
pISSN - 1549-1277
DOI - 10.1371/journal.pmed.0030096
Subject(s) - virology , rna interference , japanese encephalitis , encephalitis , small hairpin rna , biology , virus , small interfering rna , rna , viral encephalitis , encephalitis viruses , gene , genetics
Background Japanese encephalitis virus (JEV) and West Nile virus (WNV) are neurotropic flaviviruses that can cause acute encephalitis with a high fatality rate. Currently there is no effective treatment for these infections. Methods and Findings We tested RNA interference (RNAi)-based intervention to suppress lethal JE and WN encephalitis in mice. To induce RNAi, we used either lentivirally expressed short hairpin RNA (shRNA) or synthetic short interfering RNA (siRNA). As target, we selected the cd loop-coding sequence in domain II of the viral Envelope protein, which is highly conserved among all flaviviruses because of its essential role in membrane fusion. Using as a target a species-specific sequence in the cd loop that is conserved only among the different strains of either JEV or WNV, we could achieve specific protection against the corresponding virus. However, by targeting a cross-species conserved sequence within the cd loop, we were able to protect mice against encephalitis induced by both viruses. A single intracranial administration of lentivirally delivered shRNA or lipid-complexed siRNA before viral challenge or siRNA treatment after viral challenge was sufficient for protection against lethal encephalitis. Conclusions RNAi-based intervention affords near complete protection from both JEV- and WNV- induced encephalitis in mice. Our results show, to our knowledge for the first time, that siRNA can be used as a broad-spectrum antiviral agent for treating encephalitis caused by multiple related viruses.