High glucose enhances HIV entry into T cells through upregulation of CXCR4

[摘要] ItiswellknownthatpatientswithHIVarepronetodiabetesmellitusbecauseofthesideeffectsofHARRT.However,whetherhighglucoseaffectstheHIVinfectionofTcellsisnotclear.RecentstudieshaveshownthatupregulationofGLUT‐1rendersTcellssusceptibletoHIVinfection.WehypothesizedthathyperglycemiahasthepotentialtoincreaseHIVinfectionbyenhancingitsentryintoimmunecells.TheeffectofhighglucoseonHIVentryintoTcells(JurkatcellsandPBMCs)andthemechanismsinvolvedwereinvestigated.HighglucosesignificantlyenhancedHIVentry,whichwasassociatedwithincreasedT‐cellexpressionofCXCR4.However,TcellswithsilencedHIF‐1αdisplayedattenuatedexpressionofCXCR4,whereasTcellswithsilencedCXCR4showeddecreasedHIVentryinahigh‐glucosemilieu.Ontheonehand,highglucosestimulatedT‐cellROSgeneration,andH2O2atlowconcentrationsenhancedtheentryofHIVintoTcells.Ontheotherhand,inhibitionofROSnotonlyattenuatedhigh‐glucose–mediatedT‐cellexpressionofCXCR4andHIF‐1αbutalsomitigatedT‐cellHIVentryinahigh‐glucosemilieu.Inourstudy,highglucoseenhancedHIVentryintoTcellsbyincreasingexpressionofCXCR4andHIF‐1α...

[学科分类] 生理学

[关键词] ROS;HIF‐1αLTR;receptors;Jurkat cells;antioxidants;enzymes