Antiretroviral Pre-exposure Prophylaxis Prevents Vaginal Transmission of HIV-1 in Humanized BLT Mice 英文参考文献.docVIP
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Antiretroviral Pre-exposure Prophylaxis Prevents Vaginal Transmission of HIV-1 in Humanized BLT Mice 英文参考文献
o
PL SMEDICINE
AntiretroviralPre-exposureProphylaxis
PreventsVaginalTransmissionofHIV-1
inHumanizedBLTMice
Paul W. Denton1,Jacob D.Estes2,Zhifeng Sun1,Florence A.Othieno1,Bangdong L.Wei1,Anja K. Wege1,
Daniel A.Powell1,Deborah Payne3,Ashley T.Haase2,J.Victor Garcia1*
1 Department of Internal Medicine, Division of Infectious Diseases, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, United States of America,
2DepartmentofMicrobiology,MedicalSchool,UniversityofMinnesota,Minneapolis,Minnesota,UnitedStatesofAmerica,3DepartmentofPathology,UniversityofTexas
SouthwesternMedicalCenteratDallas,Dallas,Texas,UnitedStatesofAmerica
Funding:Thisworkhasbeen
supportedinpartwithfederalfunds
fromNationalInstituteofAllergy
andInfectiousDiseases,National
InstitutesofHealth(NIH)grants
AI028246(ATH),AI071940,
CA082055andAI039416(JVG),and
theDepartmentofObstetricsand
Gynecology’sTissueProcurement
FacilityoftheUniversityofTexas
SouthwesternMedicalCenterat
Dallas(NIHgrantHD011149).The
fundershadnoroleinstudydesign,
datacollection,andanalysis,
ABSTRACT
Background
Worldwide,vaginaltransmissionnowaccountsformorethanhalfofnewlyacquiredHIV-1
infections. Despite the urgency to develop and implement novel approaches capable of
preventing HIV transmission, this process has been hindered by the lack of adequate small
animalmodelsforpreclinicalefficacyandsafetytesting.Giventheimportanceofthisrouteof
transmission, we investigated the susceptibility of humanized mice to intravaginal HIV-1
infection.
decisiontopublish,orpreparation
ofthemanuscript.
MethodsandFindings
CompetingInterests:Theauthors
havedeclaredthatnocompeting
interestsexist.
Weshowthatthefemalereproductivetractofhumanizedbonemarrow–liver–thymus(BLT)
mice is reconstituted with human CD4t T and other relevant human cells, rendering these
humanizedmicesusceptibletointravaginalinfectionbyHIV-1.EffectsofHIV-1infectioninclude
CD4t T cell depletion in gut-associated lymphoid tissue (GALT) that closely mimics what
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