Molecular Characterization of HIV-1 CRF01_AE in Mekong Delta, Vietnam, and Impact of T-Cell Epitope Mutations on HLA Recognition (ANRS 12159) 英文参考文献.docVIP

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Molecular Characterization of HIV-1 CRF01_AE in Mekong Delta, Vietnam, and Impact of T-Cell Epitope Mutations on HLA Recognition (ANRS 12159) 英文参考文献.doc

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Molecular Characterization of HIV-1 CRF01_AE in Mekong Delta, Vietnam, and Impact of T-Cell Epitope Mutations on HLA Recognition (ANRS 12159) 英文参考文献

MolecularCharacterizationofHIV-1CRF01_AEin MekongDelta,Vietnam,andImpactofT-CellEpitope MutationsonHLARecognition(ANRS12159) EstibalizLazaro1.,LuongThuTram2.,PantxikaBellecave1,Gwenda-LineGuidicelli3,GuerricAnies3,4, HuynhHoangKhanhThu2,MariePillotDebelleix1,MurielVray5,PatriciaRecordon-Pinson1 ,Jean-Luc Taupin3,4,TruongThiXuanLien2,HerveFleury1* 1LaboratoiredeVirologie,CHUdeBordeauxetCNRS-UMR5234,Universite′ VictorSegalen-Bordeaux2,Bordeaux,France,2PasteurInstitute,HoChiMinhCity,Vietnam, 3Laboratoire d’immunologie et immunoge′ne′tique, CHU de Bordeaux, Bordeaux, France, 4CNRS-UMR 5164, Universite′ Victor Segalen-Bordeaux 2, Bordeaux, France, 5InstitutPasteur,Paris,France Abstract Background: To date, 11 HIV-1 subtypes and 48 circulating recombinant forms have been described worldwide. The underlying reason why their distribution is so heterogeneous is not clear. Host genetic factors could partly explain this distribution.TheaimofthisstudywastodescribeHIV-1strainscirculatinginanunexploredareaofMekongDelta,Vietnam, andtoassesstheimpactofoptimalepitopemutationsonHLAbinding. Methods:Werecruited125chronicallyantiretroviral-naiveHIV-1-infectedsubjectsfromfivecitiesintheMekongDelta.We performed high-resolution DNA typing of HLA class I alleles, sequencing of Gag and RT-Prot genes and phylogenetic analysisofthestrains.EpitopemutationswereanalyzedinpatientsbearingtheHLAallelerestrictingthestudiedepitope. Optimalwild-typeepitopesfromtheLosAlamosdatabasewereusedasreference.T-cellepitoperecognitionwaspredicted using the immune epitope database tool according to three different scores involved in antigen processing (TAP and proteasomescores)andHLAbinding(MHCscore). Results: All sequences clustered with CRF01_AE. HLA class I genotyping showed the predominance of Asian alleles as A*11:01andB*46:01withaVietnamesespecificityheldbytwodifferenthaplotypes.Thepercentageofhomologybetween MekongandBconsensusHIV-1sequenceswasabove85%.DivergentepitopeshadTAPandproteasomescorescompara