Anti-HIV Activity of Human Defensin 5 in Primary CD4+ T Cells under Serum-Deprived Conditions Is a Consequence of Defensin-Mediated Cytotoxicity.docVIP

Anti-HIV Activity of Human Defensin 5 in Primary CD4+ T Cells under Serum-Deprived Conditions Is a Consequence of Defensin-Mediated Cytotoxicity.doc

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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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