HIVinfectionleadstodrasticdeclinesinCD4Thelpercells,inpartthroughapoptosisofuninfectedcells.ApoptosisofuninfectedcellsmaybeinducedthroughtheexpressionofFasligandonthesurfaceofHIV-infectedcells,stimulatingtheFas-dependentapoptoticpathwayincellsthatcomeincontactwithinfectedcells.TheNEFproteinexpressedbyHIVmayplayinducetheexpressionofFas-ligandbyinfectedcells.Ifthisisthecase,thenaquestionthatarisesishowinfectedcellsthemselvesescapeFas-mediatedapoptosis.TheNEFproteinappearstoplayaroleinthisprocessaswell.NEFinteractswiththeASK1kinase(apoptosissignal-regulatingkinase)involvedinapoptoticsignalingbyTNFandFas-ligand.InteractionofNEFwithASK1preventsphosphorylationofdownstreamMAPkinasesandJNKkinasesinvolvedinapoptoticsignaling.

Contributor:GlennCroston,PhD

REFERENCES:XiaoX.,ScreatonG.HIV-INef:negativeeffectorofFas?NatureImmunology2001Vol2(5):pp384-385

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