Severe Hemorrhagic Fever in Strain 13N Guinea Pigs Infected with Lujo Virus 英文参考文献.docVIP

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Severe Hemorrhagic Fever in Strain 13N Guinea Pigs Infected with Lujo Virus 英文参考文献.doc

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Severe Hemorrhagic Fever in Strain 13N Guinea Pigs Infected with Lujo Virus 英文参考文献

SevereHemorrhagicFeverinStrain13/NGuineaPigs InfectedwithLujoVirus BrianH.Bird1*,KimberlyA.Dodd1,2,BobbieR.Erickson1,Ce′sarG.Albarin?o1,AyanK.Chakrabarti1, LauraK.McMullan1,EricBergeron1,UteStro¨eher1,DeborahCannon1,BrockMartin1,JoAnnD.Coleman- McCray1,StuartT.Nichol1,ChristinaF.Spiropoulou1* 1ViralSpecialPathogensBranch,DivisionofHighConsequencePathogensandPathology,CentersforDiseaseControlandPrevention,Atlanta,Georgia,UnitedStatesof America,2SchoolofVeterinaryMedicine,UniversityofCaliforniaDavis,Davis,California,UnitedStatesofAmerica Abstract Lujovirus(LUJV)isanovelmemberoftheArenaviridaefamilythatwasfirstidentifiedin2008afteranoutbreakofsevere hemorrhagic fever (HF). In what was a small but rapidly progressing outbreak, this previously unknown virus was transmittedfromthecriticallyillindexpatientto4attendinghealthcareworkers.Fourpersonsdiedduringthisoutbreak,for atotalcasefatalityof80%(4/5).ThesuspectedrodentsourceoftheinitialexposuretoLUJVremainsamystery.Becauseof theeaseoftransmission,highcasefatality,andnovelnatureofLUJV,wesoughttoestablishananimalmodelofLUJVHF. Initialattemptsinmicefailed,butinfectionofinbredstrain13/Nguineapigsresultedinlethaldisease.Atotalof41adult strain13/Nguineapigswereinfectedwitheitherwild-typeLUJVorafull-lengthrecombinantLUJV.Resultsdemonstrated thatstrain13/NguineapigsprovideanexcellentmodelofsevereandlethalLUJVHFthatcloselyresembleswhatisknown of the human disease. All infected animals experienced consistent weight loss (3–5% per day) and clinical illness characterized by ocular discharge, ruffled fur, hunched posture, and lethargy. Uniform lethality occurred by 11–16 days post-infection.AllanimalsdevelopeddisseminatedLUJVinfectioninvariousorgans(liver,spleen,lung,andkidney),and leukopenia, lymphopenia, thrombocytopenia, coagulopathy, and elevated transaminase levels. Serial euthanasia studies revealedatemporalpatternofvirusdisseminationandincreasingseverityofdisease,primarilytargetingtheliver,spleen, lungs,andlowergastrointestinalt