Medical Microbiology

390 7 GeneralVirology

Mutation.Mutationsarechangesinthebasesequenceofanucleicacid,re-

sultinginamoreorlessradicalalterationoftheresultingprotein.So-called

“silentmutations”(inthesecondorthirdnucleotideofacodon)donotin-

fluencetheaminoacidsequenceoftheprotein.

Medicallyimportantaremutantswithweakenedvirulencethathavere-

tainedtheirantigenicityandreplicationcapabilitiesintact.Theseareknown

as“attenuated”viruses.Theyaretherawmaterialoflivevaccines.

Recombination.Theviralreplicationprocessincludesproductionofalarge

numberofcopiesoftheviralnucleicacid.Incaseswheretwodifferentviral

strainsarereplicatinginthesamecell,thereisachancethatstrandbreakage

andreunionwillleadtonewcombinationsofnucleicacidsegmentsorex-

changesofgenomesegments(influenza),sothatthegeneticmaterialisre-

distributedamongtheviralstrains(recombination).Newgeneticproperties

willthereforebeconferreduponsomeoftheresultingviralprogeny,someof

whichwillalsoshowstableheritability.Geneticmaterialcanalsobeex-

changedbetweenvirusandhostcellbythesamemechanismorbyinsertion

ofall,orpart,oftheviralgenomeintothecellgenome.

VirusesasVectors

Thenaturalprocessesofgenetransferbetweenvirusesandtheirhostcellsde-

scribedabovecanbeexploitedtogivecertaincellsnewcharacteristicsbyusing

thevirusesasvectors.IfthevectorDNAcarryingthedesiredadditionalgeneinte-

gratesstablyinthehostcellgenome(e.g.,retroviruses,adenoviruses,ortheade-

noassociatedvirus),thehostcellispermanentlychanged.Thiscanbecomethe

basisfor“genetherapy”ofcertainfunctionaldisorderssuchascysticfibrosisor

parkinsonism.Nonintegratingvectors(alphaviruses,e.g.,theSindbisvirus,mengo-

virus,orvacciniavirus)resultintemporaryexpressionofacertainprotein,which

canbeused,forinstance,toimmunizeahostorganism.Bythismeans,wildfoxes

canbevaccinatedagainstrabiesusingavacciniavirusthatexpressesarabiesvirus

glycoprotein.Suchexperimentalworkmustofcoursealwayscomplywithnational

lawsonthereleaseofgeneticallyengineeredmicroorganisms.Itmustalsobemen-

tionedherethatonlysomaticgenetherapycanbeconsideredforuseinhumans.

Humangermlinetherapyusingthemethodsofgeneticengineeringisgenerally

rejectedasunethical.

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Kayser, Medical Microbiology © 2005 Thieme