SnapShot:varGeneExpressionintheMalariaParasiteArturScherf,LoïcRivière,andJoseJuanLopez-RubioInstitutPasteurCNRSURA2581,Paris,France190Cell134,July11,2008©2008ElsevierInc.DOI10.1016/j.cell.2008.06.042Seeonlineversionforlegend,abbreviations,andreferences.SnapShot:varGeneExpressionintheMalariaParasiteArturScherf,LoïcRivière,andJoseJuanLopez-RubioInstitutPasteurCNRSURA2581,Paris,France190.e1Cell134,July11,2008©2008ElsevierInc.DOI10.1016/j.cell.2008.06.042AnimportantsurvivalstrategyfortheprotozoanparasitePlasmodiumfalciparum,whichcausesmalariainhumans,reliesonitsabilitytoevadethehostimmuneresponse.ItdoessoprincipallybyexpressingavariantsurfaceadhesionmoleculecalledPfEMP1.About60membersofthevargenefamilyencodethevariantPfEMP1protein.(A)PfEMP1isexportedviavesicle-likestructures(Maurer´sclefts)totheplasmamembraneoftheinfectedredbloodcellandassociateswithaparasite-derivedelectron-denseprotrusioncalledtheknobonthehosterythrocytesurface.PfEMP1mediatesadhesionofinfectederythrocytestoreceptorsonendothelialcellsandotherhostcells.(B)Eachindividualparasiteexpressesasinglevargeneatanyonetime,maintainingallothermembersofthevargenefamilyinatranscriptionallysilentstateusingaprecisecountingmechanismthathasyettobeelucidated.Thegreatestlevelofvargenetranscriptionoccursinearlyringstageparasites(4–10hrpost-erythrocyteinvasion;thetotalcycletimeis48hr).Inthelaterstageparasites(schizonts),vargenesarenottranscribed.Regulationoccursattheleveloftranscriptionalinitiationinamonoallelicmanner.Thesamevargeneisexpressedduringmanyparasitegenerations.Switchingexpressiontoanothervariant,PfEMP1avoidsimmuneclearanceandprolongsinfection.Fastandslowswitchingrateshavebeenobservedinparasitesinvitro.vargenesexhibitingfastswitchingtendtobelocatedinsubtelomericregionsofchromosomes.(C)ThemajorityofP.falciparumvargenesarelocatedinthehighlypolymorphicendsofthe14parasitechromosomes.Theyarelocatedimmediatelyadjacenttothenoncodingsubtelomericregionscomposedofamosaicofsixdistincttelomere-associatedrepeateleme...
