Medical Microbiology

DefenseMechanisms 401

substanceshavethesameeffect:theyderepressthecellularinterferongene,

inducingthecelltobeginproducinginterferonprecursors.Followingglyco-

sylation,thefinishedinterferonisreleasedintothesurroundingareaand

bindstotheinterferonreceptorofthenearestcell.Thepresenceorlackof

thisreceptordetermineswhateffecttheinterferonwillhave.Italsoexplains

themoreorlesspronouncedlyspecies-specificnatureofthecell-to-interfer-

onrelationship.Inprinciple,theeffectofinterferonisstrongestwithinthe

speciesinwhichitwasproduced.Withintherecipientor“target”cellthe

interferoninducestheexpressionoftheso-calledinterferon-stimulatedgenes

(ISG)bymeansofasignalcascade,theresultofwhichistoinhibitviralre-

plication.

Interferon-InducedProteins

(2’-5’)(A)nsynthetase.Thiscellularenzymeisfirstproducedinaninactiveform.

Itisthenactivatedbydouble-strandedRNA,afterwhichitcanpolymerizeoligo-

adenylateoutofATP.Thisproductthenactivatesacellularribonuclease(RNaseL),

whichinactivatesviral(andcellular)mRNA.

P1/eIF-2kinase.Thiscell-codedkinaseisalsoinactiveinitsnativestateandmust

alsobeactivatedbydsRNA.Itisthenabletophosphorylatetheribosomalprotein

P1andtheinitiationfactoreIF-2,resultingininhibitionofproteinsynthesisinitia-

tion.

Howviralandcellularproteinsynthesisaretoldapartinthiskinaseactivation

processisnotquiteclear.PerhapsthedsRNAneededtoactivatetheenzymeis

thekey:thissubstanceislackinginnoninfectedcellsandisonlyproducedincells

infectedbyan(RNA)virus,sothattheantiviralenzymescanonlybeactivatedin

theinfectedcells.

Mxprotein.Theobservationthatcertainmiceareresistanttoinfluenza

virusesledtothediscoveryoftheinterferon-induced, 75 – 80 kDaMxproteins

codedforbydominanthereditaryMxgenes.Mxproteinsaccumulatein

mousecellnucleiandinhibitthemRNAsynthesisofinfluenzaviruses.

Mx-micearekilledbyinfluenza.Inhumans,Mxproteinsaccumulatein

thecytoplasm,buttheirmechanismofactionisunknown.

SpecificImmuneDefenses

Thespecific,adaptiveimmunedefensesincludeboththehumoralsystem

(antibody-producingBcells)andthecellularsystem(Thelpercellsandcy-

totoxicTlymphocytes).Ingeneral,virusestheantigensofwhichareex-

pressedonthesurfaceoftheinfectedcellstendtoinduceacellularimmune

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Kayser, Medical Microbiology © 2005 Thieme