Sialoadhesin Expressed on IFN-Induced Monocytes Binds HIV-1 and Enhances Infectivity 英文参考文献.docVIP

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Sialoadhesin Expressed on IFN-Induced Monocytes Binds HIV-1 and Enhances Infectivity 英文参考文献.doc

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Sialoadhesin Expressed on IFN-Induced Monocytes Binds HIV-1 and Enhances Infectivity 英文参考文献

SialoadhesinExpressedonIFN-InducedMonocytesBinds HIV-1andEnhancesInfectivity HansRempel1,CyrusCalosing1,BingSun1,LynnPulliam1,2* 1DepartmentofLaboratoryMedicineattheVeteransAffairsMedicalCenter,SanFrancisco,California,UnitedStatesofAmerica,2UniversityofCaliforniaSanFrancisco, SanFrancisco,California,UnitedStatesofAmerica Abstract Background: HIV-1 infection dysregulates the immune system and alters gene expression in circulating monocytes. DifferentialgeneexpressionanalysisofCD14 monocytesfromsubjectsinfectedwithHIV-1revealedincreasedexpression + of sialoadhesin (Sn, CD169, Siglec 1), a cell adhesion molecule first described in a subset of macrophages activated in chronicinflammatorydiseases. Methodology/PrincipalFindings:WeanalyzedsialoadhesinexpressiononCD14+monocytesbyflowcytometryandfound significantlyhigherexpressioninsubjectswithelevatedviralloadscomparedtosubjectswithundetectableviralloads.In cultured CD14+ monocytes isolated from healthy individuals, sialoadhesin expression was induced by interferon-a and interferon-cbutnottumornecrosisfactor-a.Usingastringentbindingassay,sialoadhesin-expressingmonocytesadsorbed HIV-1throughinteractionwiththesialicacidresiduesontheviralenvelopeglycoproteingp120.Furthermore,monocytes expressingsialoadhesinfacilitatedHIV-1transinfectionofpermissivecells,whichoccurredintheabsenceofmonocyteself- infection. + Conclusions/Significance:IncreasedsialoadhesinexpressiononCD14 monocytesoccurredinresponsetoHIV-1infection withmaximumexpressionassociatedwithhighviralload.WeshowthatinterferonsinducesialoadhesininprimaryCD14+ monocytes,whichisconsistentwithanantiviralresponseduringviremia.Ourfindingssuggestthatcirculatingsialoadhesin- expressingmonocytesarecapableofbindingHIV-1andeffectivelydeliveringvirustotargetcellstherebyenhancingthe distribution of HIV-1. Sialoadhesin could disseminate HIV-1 to viral reservoirs during monocyte immunosurveillance or migrationtositesofinflammationandthenfacilitateHIV-1infectionofpermissivecells.