Anti-HIV Activity of Human Defensin 5 in Primary CD4+ T Cells under Serum-Deprived Conditions Is a Consequence of Defensin-Mediated Cytotoxicity.docVIP
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Anti-HIVActivityofHumanDefensin5inPrimaryCD4TCellsunderSerum-DeprivedConditionsIsaConsequenceofDefensin-MediatedCytotoxicity
Anti-HIVActivityofHumanDefensin5inPrimaryCD4+T
CellsunderSerum-DeprivedConditionsIsa
ConsequenceofDefensin-MediatedCytotoxicity
JianDing1,CarleyTasker2,4,KimyataValere2,4,TiinaSihvonen1,DanteB.Descalzi-Montoya3,4,
WuyuanLu5,TheresaL.Chang1,2*
1PublicHealthResearchInstitute,RutgersBiomedicalandHealthSciences-NewJerseyMedicalSchool,Newark,NewJersey,UnitedStatesofAmerica,2Departmentof
MicrobiologyandMolecularGenetics,RutgersBiomedicalandHealthSciences-NewJerseyMedicalSchool,Newark,NewJersey,UnitedStatesofAmerica,3Departmentof
Pathology and Laboratory Medicine, Rutgers Biomedical and Health Sciences-New Jersey Medical School, Newark, New Jersey, United States of America, 4Graduate
SchoolofBiomedicalSciences,RutgersBiomedicalandHealthSciences-NewJerseyMedicalSchool,Newark,NewJersey,UnitedStatesofAmerica,5InstituteofHuman
VirologyandDepartmentofBiochemistryandMolecularBiology,UniversityofMarylandSchoolofMedicine,Baltimore,Maryland,UnitedStatesofAmerica
Abstract
Background:Wehavepreviouslyshownthathumandefensin5(HD5)promotesHIVinfectivityinbothprimaryCD4+Tcells
and HeLa cells expressing CD4 and CCR5. HD5 is induced in response to sexually transmitted infections (STIs) such as
Chlamydia trachomatis and Neisseria gonorrhoeae, suggesting it plays a role in STI-mediated enhancement of HIV
transmission.Incontrasttoourfindings,arecentstudyreportsthatHD5hasananti-HIVeffectinprimaryCD4+Tcellsunder
serum-deprived conditions. To resolve these apparently contradictory observations, we investigated experimental
parametersthatmightcontributetocontrastingeffectsofHD5.
Results:Serum-deprivedcultureconditionswereassociatedwithanti-HIVactivity.IncontrasttothedependenceoftheHIV
enhancingeffectonHD5structure,theanti-HIVactivityinserum-deprivedprimaryCD4+TcellswasindependentofHD5
structureasthelinearpeptide[Abu]HD5exhibitedsimilaranti-HIVactivity.Underserumdeprivedconditions,HD5blocked
CD4-receptor-independent HIV-1 infection before or after viral entry. We found that HD5 and its linear f
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