Medical Microbiology

DNAViruses 419

BiologyoftheHerpesviruses

Severalhundredherpesvirusspecieshavebeendescribedinhumansandanimals,

allwiththesamemorphology(Fig.8.4a).TheyhavedsDNAgenomes.Replicationof

theDNAandthemorphogenesisofthevirusparticletakeplaceinthehost-cell

nucleus.Theenvelope(innernuclearmembrane)isthenformedwhenthevirus

penetratesthenuclearmembrane(Fig.8.4b),wherebydependingonthecell

andviraltypeinvolvedamoreorlesssubstantialnumberofvirusesreceiveanen-

velopeafterreachingthecytoplasm,atthecellmembraneornotatall.Theenve-

lopeisthemajordeterminantofviralinfectivity(seeChapter 7 ,p. 3 78f.).Sincethe

envelopecontainsmainlyhost-celldeterminants,itcanalsobeassumedthatit

providesalevelofprotectionfromhostimmuneresponses.

Commontoallherpesvirusesisahighlevelofgeneralizedcontamination(60– 90 %

carriers)andtheabilitytopersistinalatentstateinthebodyoverlongperiods.The

differentviralspeciespersistindifferentcells,wherebythecelltypeisthedecisive

factordetermininglatencyorreplicationofthevirus.Herpessimplexvirusandvar-

icella-zostervirusdonotproduceanyvirusparticlesduringlatency,althoughthey

doproduceone,orafew,mRNAtypesandthecorrespondingproteins.Cytome-

galovirusandEpstein-Barrvirusappeartomaintaincontinuousproductionofsmall

numbersofvirusesaswell,sothatfreshinfectionofasmallnumberofnewcellsis

anongoingprocess.Theseviruseswouldappeartoproducepersistent,subclinical

infectionsconcurrentlywiththeirlatentstatus(p.394).Reactivationoftheselatent

virusesisapparentlyinitiatedbyanumberoffactors(psychologicalstress,solar

irradiation,fever,traumata,otherinfections,immunosuppressivetherapy),but

theactualmechanismsthatreactivatethelyticvirallifecycleareunknown.

Humanherpesviruses(withtheexceptionofthevaricella-zostervirus)andmany

zoopathicherpesspecieshavealsobeenimplicatedintheetiologyofmalignancies.

Eighthumanherpesvirusesthatinfectdifferentorgansareknowntodate,

e.g.,theskin(herpessimplexvirustypes 1 and2,varicella-zostervirus),the

lymphaticsystem(Epstein-Barrvirus,humanherpesvirustype6,cytomega-

loviruses),andtheCNS(herpessimplexvirus,cytomegalovirus).

HerpessimplexVirus(HSV)

Pathogen,pathogenesis,andclinicalpicture.Theviralgenomecodesfor

about 90 proteins,categorizedas“immediateearly”(regulatoryfunctions),

“early”(DNAsynthesis),and“late”(structural)proteins.Herpessimplex

virusesareclassifiedintypes 1 and2,whichdifferbothserologicallyand

biologically(host-cellspectrum,replicationtemperature).Initialinfection

withherpessimplextype 1 usuallyoccursinearlychildhood.Theportal

ofentryisnormallytheoralmucosa(“oraltype”)andtheinfectionusually

manifestsasagingivostomatitis.Thevirusesthenwanderalongaxonsinto

theCNS,wheretheypersistinalatentstateinthetrigeminal(Gasseri)gang-

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Kayser, Medical Microbiology © 2005 Thieme