A Single siRNA Suppresses Fatal Encephalitis Induced by Two Different Flaviviruses 英文参考文献.docVIP

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A Single siRNA Suppresses Fatal Encephalitis Induced by Two Different Flaviviruses 英文参考文献.doc

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A Single siRNA Suppresses Fatal Encephalitis Induced by Two Different Flaviviruses 英文参考文献

o PL SMEDICINE ASinglesiRNASuppressesFatalEncephalitis InducedbyTwoDifferentFlaviviruses Priti Kumar1,Sang Kyung Lee2,Premlata Shankar1*,N.Manjunath1* 1 The CBR Institute for Biomedical Research and Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, United States of America, 2 Department of Bioengineering,HanyangUniversity,Seoul,Korea Funding:Thisworkwassupported byNIHgrantU19AI056900toNM andPS. ABSTRACT Background CompetingInterests:Theauthors havedeclaredthatnocompeting interestsexist. Japaneseencephalitisvirus(JEV)andWestNilevirus(WNV)areneurotropicflavivirusesthat cancauseacuteencephalitiswithahighfatalityrate.Currentlythereisnoeffectivetreatment fortheseinfections. AcademicEditor:CliffordLane, NationalInstitutesofHealth,United StatesofAmerica MethodsandFindings Citation:KumarP,LeeSK,Shankar P,ManjunathN(2006)AsinglesiRNA suppressesfatalencephalitis inducedbytwodifferentflaviviruses. PLoSMed3(4):e96. We tested RNA interference (RNAi)-based intervention to suppress lethal JE and WN encephalitis inmice.ToinduceRNAi,weusedeitherlentivirallyexpressedshorthairpinRNA (shRNA)orsyntheticshortinterferingRNA(siRNA).Astarget,weselectedthecdloop-coding sequence in domain II of the viral Envelope protein, which is highly conserved among all flavivirusesbecauseofitsessentialroleinmembranefusion.Usingasatargetaspecies-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 targetingacross-speciesconservedsequencewithinthecdloop,wewereabletoprotectmice againstencephalitisinducedbybothviruses.Asingleintracranialadministrationoflentivirally deliveredshRNAorlipid-complexedsiRNAbeforeviralchallengeorsiRNAtreatmentafterviral challengewassufficientforprotectionagainstlethalencephalitis. Received:September20,2005 Accepted:December16,2005 Published:February14,2006 DOI: 10.1371/journal.pmed.0030096 Copyright:ó2006Kumaretal.This isano