Attenuation of HIV‐1 replication in macrophages by cannabinoid receptor 2 agonists

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: neuroinflammation;    JWH133;    CXCR4;    CCR5;    encephalitis;    CB2;   

DOI  :  10.1189/jlb.1012523

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

InfiltratingmonocytesandmacrophagesplayacrucialroleintheprogressionofHIV‐1infectionintheCNS.PreviousstudiesshowedthatactivationoftheCB2canattenuateinflammatoryresponsesandaffectHIV‐1infectivityinTcellsandmicroglia.Here,wereportthatCB2agonistscanalsoactasimmunomodulatorsonHIV‐1‐infectedmacrophages.First,ourfindingsindicatedthepresenceofelevatedlevelsofCB2expressiononmonocytes/macrophagesinperivascularcuffsofpostmortemHIV‐1encephaliticcases.InvitroanalysisbyFACSofprimaryhumanmonocytesrevealedastep‐wiseincreaseinCB2surfaceexpressioninmonocytes,MDMs,andHIV‐1‐infectedMDMs.Wenexttestedthenotionthatup‐regulationofCB2mayallowfortheuseofsyntheticCB2agonisttolimitHIV‐1infection.TwocommerciallyavailableCB2agonists,JWH133andGP1a,andaresorcinol‐basedCB2agonist,O‐1966,wereevaluated.ResultsfrommeasurementsofHIV‐1RTactivityintheculturemediaof7day‐infectedcellsshowedasignificantdecreaseinRTactivitywhentheCB2agonistwaspresent.Furthermore,CB2activationalsopartiallyinhibitedtheexpressionofHIV‐1pol.CB2agonistsdidnotmodulatesurfaceexpressionofCXCR4orCCR5detectedbyFACS.WespeculatethatthesefindingsindicatethatpreventionofviralentryisnotacentralmechanismforCB2‐mediatedsuppressioninviralreplication.However,CB2mayaffecttheHIV‐1replicationmachinery.Resultsfromasingle‐roundinfectionwiththepseudotypedvirusrevealedamarkeddecreaseinHIV‐1LTRactivationbytheCB2ligands.Together,theseresultsindicatethatCB2mayofferameanstolimitHIV‐1infectioninmacrophages...

【 授权许可】

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