Medical Microbiology

396 7 GeneralVirology

position,theLTRcanalsoinduceheightenedexpressivityincellularproto-

oncogenes(“promoterinsertionhypothesis”or“insertionmutagenicity”),

whichcanleadtotheformationoftumors.Thisisaslowprocess(e.g.,chronic

leukemias)inwhichcocarcinogenscanplayanimportantrole.Thetrans-

formedcellsproducenewviruses.

&Retroviruseswithanoncogene:aviraloncogenealwaysrepresentsa

changedstatecomparedwiththeoriginalcellularproto-oncogene(deletion,

mutation).Itisintegratedinthecellgenometogetherwiththeresidualviral

genome(parts)afterreversetranscription,andthenexpressedunderthe

influenceoftheLTR,inmostcasesoverexpressed.Thisleadstorapiddevel-

opmentofacutemalignanciesthatproducenonewviruses.

Overproductionofoncogeneproductscanbecompensatedbygeneproducts

fromantioncogenes.Thelossormutationofsuchasuppressorgenecan

thereforeresultintumorformation.

DNATumorViruses

GeneshavealsobeenfoundinDNAtumorvirusesthatinduceamalignant

transformationofthehostcell.Incontrasttotheoncogenesinoncoviruses,

thesearegenuineviralgenesthathavepresumablydevelopedindependently

ofoneanotheroveramuchlongerevolutionaryperiod.Theycodeforviral

regulatorproteins,whichareamongtheso-calledearlyproteins.Theyare

producedearlyintheviralreplicationcycleandassumeessentialfunctions

inviralDNAreplication.Theironcogenicpotentialderivesamongother

thingsfromthefactthattheybindtotheproductsoftumorsuppressorgenes

suchasp53,Rb(antioncogenes,“antitransformationproteins”seeabove)

andcanthusinhibittheirfunctions.DNAvirusesaremoreimportantindu-

cersofhumantumorsthanoncoviruses(example:HHV8,papovaviruses,

hepatitisBviruses,Epstein-Barrviruses).

Pathogenesis

&Theterm“pathogenesis”coversthefactorsthatcontributetotheorigins

anddevelopmentofadisease.Inthecaseofviruses,theinfectionisbyapar-

enteralormucosalroute.Theviruseseitherreplicateattheportalofentry

only(localinfection)orreachtheirtargetorganhematogenously,lympoge-

nouslyorbyneurogenicspread(generalizedinfection).Inbothcases,viral

replicationinducesdegenerativedamage.Itsextentisdeterminedbythe

extentofvirus-inducedcelldestructionandsetsthelevelofdiseasemani-

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Kayser, Medical Microbiology © 2005 Thieme