Medical Microbiology

Host-CellReactions 393

tonecroticcytopathy,theirprimarypurposeistosupportspecificstepsin

viralsynthesis.Forexample,RNAsynthesisandviralassemblyinpicorna-

virusinfectionsrequiresspecific,new,virus-inducedmembranestructures

andvesiclesthatsubsequentlymanifesttheirsecondaryeffectbycausing

aCPEandeventualcelldeath.

ShutoffPhenomena

Somevirusesareabletoblock,moreorlesscompletely,stepsincellularmacromol-

eculesynthesisnotusefultothem.Herpesviruses,forexample,whichpossessDNA

polymeraseoftheirown,blockcellularDNAsynthesis.DNAreplicationinadeno-

viruses,bycontrast,isdirectlycoupledtothatofthecell.Suchshutoffphenomena

apparentlycontributetorapidandefficientviralreplicationbyeliminatingcompet-

ingcellularsyntheticprocesses.Inpolioviruses,whichinhibitbothtranscriptionand

translationinthehostcell,theshutoffprocessesareinducedbyviralproteinsthat

interferewiththerelevantregulatorymechanismsinordertoinhibittranscription

andtoinactivateinitiationfactoreIF4GII,whichisnotrequiredfortranslationof

EnterovirusmRNA,inordertoinhibittranslation.Theseshutoffphenomenaof

coursealsohaveapathogeniceffectsincetheyinhibitcellularmetabolism,but

notinsuchawayastonecessarilykillthehostcell.

Apoptosis.Cellspossessnaturalmechanismsthatinitiatetheirself-destruc-

tion(apoptosis)bymeans ofpredetermined cytoplasmic andnuclear

changes.Infectionswithsomevirusesmayleadtoapoptosis.Inrapidlyre-

plicatingviruses,theviralreplicationprocessmustbedeceleratedtoallow

theslow,energy-dependentprocessofapoptosistorunitscoursebeforethe

cellisdestroyedbyvirus-inducednecrosis.Thebodyrapidlyeliminates

apoptoticcellsbeforeaninflammatoryreactioncandevelop,whichisappar-

entlywhyvirus-inducedapoptosisusedtobeoverlookedsooften.Apoptosis

canthusbeconsideredadefensemechanism,althoughcertainvirusesare

abletoinhibitit.

VirusReplicationwithoutCellDestruction

(NoncytocidalInfection)

Thisoutcomeofinfectionisobservedwithcertainvirusesthatdonotcause

anyextensiverestructuringofthehostcellandaregenerallyreleasedby

“budding”atthecellsurface.Thismodeofreplicationisseen,forexample,

intheoncornavirusesandmyxovirusesandinthechronicformofhepatitisB

virusinfection.However,celldestructioncanfollowasasecondaryresultof

infection,however,iftheimmunesystemrecognizesviralantigensonthecell

surface,classifiesitas“foreign”anddestroysit.

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Kayser, Medical Microbiology © 2005 Thieme