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Defective interfering virus protects elderly mice from influenza.doc

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Defective interfering virus protects elderly mice from influenza

Scottetal.VirologyJournal2011,8:212 /content/8/1/212 RESEARCH OpenAccess Defectiveinterferingvirusprotectselderlymice frominfluenza PaulDScott,BoMeng,AnthonyCMarriott,AndrewJEastonandNigelJDimmock* Abstract Background:Wehaveidentifiedandcharacterisedadefective-interfering(DI)influenzaAvirusparticlescontaining ahighlydeletedsegment1RNAthathasbroad-spectrumantiviralactivity.Inyoungadultmiceitexertsprotection againstseveraldifferentsubtypesofinfluenzaAvirus(definedhereashomologousorgeneticallycompatible protection)andagainstaparamyxovirusandaninfluenzaBvirus(heterologousorgeneticallyunrelated protection).Homologousprotectionismediatedbyreplicationcompetitionbetweenthedeletedandfull-length genomes,andheterologousprotectionoccursthroughstimulationofinnateimmunity,especiallyinterferontypeI. Methods:AsingledoseoftheprotectiveDIviruswasadministeredintranasallytoelderlymiceat-7,-1and+1 daysrelativetointranasalchallengewithinfluenzaAvirus. Results:AsingledoseoftheDIvirusgiven1or7daysprotectedelderlymice,reducingasevere,sometimesfatal diseasetoasubclinicalormildinfection.Incontrast,allmembersofcontrolgroupstreatedwithinactivatedDI virusbeforechallengebecameextremelyillandmostdied.Despitethesubclinical/mildnatureoftheirinfection, protectedmicedevelopedsolidimmunitytoasecondinfectiouschallenge. Conclusions:ThedefectiveinterferingvirusiseffectiveinpreventingsevereinfluenzaAinelderlymiceandmay offeranewapproachtoprotectionofthehumanpopulation. Keywords:elderlydefective-interferingvirus,geriatric,influenza,mice,treatment Background (HRSV)arepre-eminent[16,17].Theseagentsarehighly As a result of improved standards in the home, work- contagious and cause outbreaks in domestic commu- place, nutrition, andhealthcare, theelderly arebecom- nitieswithahighlevelofmorbidityandoftenmortality. ing an ever increasing proportion of the world’s Since 1977 two subtypes of influenza A virus (H1N1 population.Yetbecauseofwaningimmunecompetence andH3N2)andaninfluenzaBvirushavebeenrespon