A Broadly Flavivirus Cross-Neutralizing Monoclonal Antibody that Recognizes a Novel Epitope within the Fusion Loop of E Protein 英文参考文献.docVIP

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A Broadly Flavivirus Cross-Neutralizing Monoclonal Antibody that Recognizes a Novel Epitope within the Fusion Loop of E Protein 英文参考文献.doc

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A Broadly Flavivirus Cross-Neutralizing Monoclonal Antibody that Recognizes a Novel Epitope within the Fusion Loop of E Protein 英文参考文献

ABroadlyFlavivirusCross-NeutralizingMonoclonal AntibodythatRecognizesaNovelEpitopewithinthe FusionLoopofEProtein Yong-QiangDeng1.,Jian-XinDai2,3.,Guang-HuiJi2.,TaoJiang1,Hua-JingWang2,3,Hai-ouYang3, Weng-LongTan3,RanLiu1,ManYu1,Bao-XueGe4,Qing-YuZhu1,E-DeQin1,Ya-JunGuo2,3* ,Cheng-Feng Qin1* 1State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China, 2International Joint Cancer Institute, Second MilitaryMedicalUniversity,Shanghai,China,3StateKeyLaboratoryofAntibodyMedicineandTargetedTherapy,Shanghai,China,4InstituteofHealthSciences,Shanghai InstitutesforBiologicalSciences,ChineseAcademyofSciences/ShanghaiJiaoTongUniversitySchoolofMedicine,Shanghai,China Abstract Flavivirusesareagroupofhumanpathogenic,envelopedRNAvirusesthatincludesdengue(DENV),yellowfever(YFV),West Nile(WNV),andJapaneseencephalitis(JEV)viruses.Cross-reactiveantibodiesagainstFlavivirushavebeendescribed,but mostofthemaregenerallyweaklyneutralizing.Inthisstudy,anovelmonoclonalantibody,designatedmAb2A10G6,was determined to have broad cross-reactivity with DENV 1–4, YFV, WNV, JEV, and TBEV. Phage-display biopanning and structure modeling mapped 2A10G6 to a new epitope within the highly conserved flavivirus fusion loop peptide, the 98DRXW101motif.Moreover,invitroandinvivoexperimentsdemonstratedthat2A10G6potentlyneutralizesDENV1–4,YFV, andWNVandconfersprotectionfromlethalchallengewithDENV1–4andWNVinmurinemodel.Furthermore,functional studiesrevealedthat2A10G6blocksinfectionatastepafterviralattachment.Theseresultsdefineanovelbroadlyflavivirus cross-reactive mAbwithhighly neutralizingactivity thatcanbe furtherdevelopedas atherapeuticagent againstsevere flavivirusinfectionsinhumans. Citation:DengY-Q,DaiJ-X,JiG-H,JiangT,WangH-J,etal.(2011)ABroadlyFlavivirusCross-NeutralizingMonoclonalAntibodythatRecognizesaNovelEpitope withintheFusionLoopofEProtein.PLoSONE6(1):e16059.doi:10.1371/journal.pone.0016059 Editor:Man-SeongPark,HallymUniversity,RepublicofKo