Medical Microbiology

Host-CellReactions 395

Oncogenes

Over 100 oncgenes(so-called“oncogenes”)havebeenfoundinthecourseof

tumorvirologyresearchtodate.Thesegenesenabletumorvirusestotransform

theirhostcellsintotumorcells.Thevarioustypesofoncogenesaredesignated

byabbreviations,inmostcasesderivedfromtheanimalspeciesinwhichthevirus

wasfirstisolated.Furtherinvestigationoftheseviraloncogeneshavenowshown

thatthesegenesarenotprimarilyofviralorigin,butarerathernormal,cellular

geneswidespreadinhumansandanimalsandacquiredbytheoncovirusesintheir

hostcells,whichcanbetransferredtonewcells(transduction).Suchacellulargene,

notoncogenicperse,iscalledaproto-oncogene.

Thenormalfunctionoftheproto-oncogenesconcernstheregulationofcellgrowth

inthebroadestsense.Theirgeneproductsaregrowthfactors,growthfactoror

hormonereceptorsandGTP-bindingorDNA-bindingproteins.Proto-oncogenes

arepotentialcontributorstotumordevelopmentthathavetobe“activated”be-

foretheycanactuallyhavesucheffects.Thiscanoccurbywayofseveraldifferent

mechanisms:

—Chromosomaltranslocation:proto-oncogenesaremovedtodifferentchromo-

somesandthusplacedundertheinfluenceofdifferentcellularpromoters,re-

sultinginachronicoverexpressionofthecorrespondingprotein.

—Mutationoftheproto-oncogene.

—Transductionoftheproto-oncogenebyanoncovirus.Theoncoviruspromoter

mayinduceoverexpressionoftheproto-oncogene,resultinginatumor.

Tumorinductionbyoncoviruses.Bothtypesofcarcinogenicretroviruses,

i.e.,thosewithnooncogeneandintactreplicationgenes(gag,pol,env,flanked

bytheLTRregions)andthosethathavebecomedefectivebytakingonan

oncogene,caninitiateatumortransformation.Onthewhole,oncoviruses

playonlyasubordinateroleinhumantumorinduction.

&Retroviruseswithoutanoncogene:LTRarehighlyeffectivepromoters.

Sincetheretrovirusgenomeisintegratedinthecellgenomeatarandom

GenomicOrganizationinOncoviruses

LTR gag pol env LTR

LTR (gag) v-onc (env) LTR

a

b

Fig. 7. 7 aAutonomouslyreproducingoncoviruseswiththethreereplication

genesgag,pol,env,flankedbytheLTRregions.

bDefectiveoncovirusescontainanoncgeneinsteadoftheentirepolregionand

partsofthegagandenvregions.

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Kayser, Medical Microbiology © 2005 Thieme