Extensive HIV-1 Intra-Host Recombination Is Common in Tissues with Abnormal Histopathology 英文参考文献.docVIP

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Extensive HIV-1 Intra-Host Recombination Is Common in Tissues with Abnormal Histopathology 英文参考文献.doc

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Extensive HIV-1 Intra-Host Recombination Is Common in Tissues with Abnormal Histopathology 英文参考文献

ExtensiveHIV-1Intra-HostRecombinationIsCommonin TissueswithAbnormalHistopathology SusannaL.Lamers1.,MarcoSalemi1,2.,DerekC.Galligan3,TuliodeOliveira1,4,GaryB.Fogel5,SaraC. Granier1,LiZhao6,JosephN.Brown2,AlannaMorris3,EliezerMasliah8,MichaelS.McGrath3,7,9* 1BioInfoExperts,Thibodaux,Louisiana,UnitedStatesofAmerica,2DepartmentofPathology,Immunology,andLaboratoryMedicine,UniversityofFlorida,Gainesville, Florida,UnitedStatesofAmerica,3DepartmentofLaboratoryMedicine,PositiveHealthProgram,UniversityofCaliforniaSanFrancisco,SanFrancisco,California,United States of America, 4South African National Bioinformatics Institute, University of the Western Cape, Cape Town, South Africa, 5Natural Selection, Inc., San Diego, California, United States of America, 6The Department of Toxicology, Shandong University, Jinan, China, 7Pathologica Inc., Burlingame, California, United States of America,8DepartmentofPathology,SchoolofMedicine,UniversityofCaliforniaSanDiego,SanDiego,California,UnitedStatesofAmerica,9AIDSandCancerSpecimen Resource,SanFrancisco,California,UnitedStatesofAmerica Abstract There is evidence that immune-activated macrophages infected with the Human Immunodeficiency Virus (HIV) are associatedwithtissuedamageandserveasalong-livedviralreservoirduringtherapy.Inthisstudy,weanalyzed780HIV geneticsequencesgeneratedfrom53tissuesdisplayingnormalandabnormalhistopathology.Wefoundupto50%ofthe sequences from abnormal lymphoid and macrophage rich non-lymphoid tissues were intra-host viral recombinants. The presence of extensive recombination, especially in non-lymphoid tissues, implies that HIV-1 infected macrophages may significantlycontributetothegenerationofelusiveviralgenotypesinvivo.Becauserecombinationhasbeenimplicatedin immune evasion, the acquisition of drug-resistance mutations, and alterations of viral co-receptor usage, any attempt towardsthesuccessfuleradicationofHIV-1requirestherapeuticapproachestargetingtissuemacrophages. Citation:LamersSL,SalemiM,GalliganDC,deOlive