Medical Microbiology

DNAViruses 431

HepatitisDpathogen.AcertainpercentageofHBV-infectedpersons,which

variesgeographically,arealsoinfectedbyasecondhepatitisvirusdiscovered

attheendoftheseventiesinItaly,thedeltaagentorhepatitisDvirus(HDV).It

wasoriginallythoughttobeanewHBVantigen.Infact,itisanunclassified

RNAvirusthatcodesforthedeltaantigen.ItscapsidconsistsofHBsantigen,

i.e.,HBV-codedmaterial.Forthisreason,theviruscanonlyreplicateinper-

sonsinfectedwithHBV(inthiscasethe“helpervirus”).

Thedeltaagentis 36 nminsizeandpossessesaveryshortviralRNAcon-

taining 1683 nucleotides.ThisRNAiscircular,hasantisense(minus)polarity

andisreminiscentinsizeandstructureoftheRNAinplantviroids(p. 47 2f.).

Itstranscriptionandreplicationtakeplaceinthecellnucleusbymeansofa

cellularpolymerase.TheresultingRNAsensestrandcontains,incontrastto

viroids,aprotein-codingsegmentcomprisingabout 800 nucleotides,which

thecellprocessesintoanmRNA.TheHDVcodesfortwoproteinswith 27 and

29 kDa(deltaantigen).Theshorterproteinwith 195 aminoacids,whichpro-

motesRNAreplication,isproducedearlierinthereplicationcycle.Later,after

thestopcodonUAGofthemRNAhasbeentransformed(enzymatically?)into

UGG,thelongerproteinwith 214 aminoacidsissynthesized;itinhibitsrep-

licationandcontrolstheencapsidationoftheHDVRNAintheHBsantigen.

Pathogenesisandclinicalpicture.TheincubationperiodofhepatitisBisfour

to 12 weeks,followedbytheacuteinfectionphase,icteric,oranictericcourse,

onceagainwithavariabledurationoftwoto 12 weeks.Thehepaticcell

damageresultingfromanHBVinfectionisnotprimarilyduetocytopathic

activityofthevirus,butrathertoahumoralandcellularimmuneresponse

directedagainstthevirus-inducedmembraneantigens(HBs,HBc)onthe

surfaceoftheinfectedhepatocytes:0.5– 1 %ofthoseinfectedexperiencea

fulminant,oftenlethal,hepatitis.In 80 – 90 %ofcasestheinfectionrunsabe-

nigncoursewithcompleterecoveryandeliminationoftheHBVfromthe

body.Achronicinfectiondevelopsin 5 – 10 %(seep.393,persistentviralin-

fections).Threeformsaredifferentiated,butmixedformsarepossible:

— healthyHBVcarriers,

— chronicpersistenthepatitis(CPH)withoutviralreplication,andfinally

— chronicaggressivehepatitis(CAH)withviralreplicationandaprogressive

course.

Achronicinfectioncanresultindevelopmentofacarcinoma(hepatocellular

carcinoma,HCC)orcirrhosisoftheliver,withincidencevaryingwidelyfrom

onegeographicareatoanother.Thedeltaagentappearstohaveanunfa-

vorableinfluenceontheclinicalcourse,usuallymakingthediseasemore

aggressive,increasingthenumberofcomplicationsandworseningtheprog-

nosis.

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Kayser, Medical Microbiology © 2005 Thieme