Medical Microbiology

Genetics 391

NongeneticInteractions

Inmixedinfectionsbytwo(ormore)viruses,variousviralcomponentscanbe

exchangedortheymaycomplement(orinterferewith)eachother’sfunctions(phe-

notypemixing,complementationorinterference).Suchprocessesdonotresultin

stableheritabilityofnewcharacteristics.

Inphenotypicmixing,thegenomeofvirusAisintegratedinthecapsidofvirusB,

oracapsidmadeupofcomponentsfromtwo(closelyrelated)virustypesisas-

sembledandthegenomeofoneofthe“parents”isintegratedinit.However,

theprogenyofsucha“mixed”virusofcourseshowsthegenotype.

Inphenotypicinterference,theprimaryinfectingvirus(usuallyavirulent)

mayinhibitthereplicationofasecondvirus,ortheinhibitionmaybemutual.

Theinterferencemechanismmaybeduetointerferonproduction(p. 40 0)or

toametabolicchangeinthehostcell.

Incomplementation,infectingviralspecieshavegeneticdefectsthat

renderreplicationimpossible.The“partner”viruscompensatesforthede-

fect,supplyingthemissingsubstancesorfunctionsinaso-calledhelperef-

fect.Inthisway,adefectiveandnondefectivevirus,ortwodefectiveviruses,

cancomplementeachother.Example:murinesarcomavirusesforwhichleu-

kemiavirushelpersdelivercapsidproteinsorthehepatitisDvirus,which

replicatesonitsownbutmustbesuppliedwithcapsidmaterialbythehe-

patitisBvirus(seeChapter8,p.429f.).

“Quasispecies.”WhenviralRNAreplicates,thereisno“proofreading”mech-

anismtocheckforcopyingerrorsasinDNAreplication.Theresultisthatthe

rateofmutationsinRNAvirusesisabout 104 ,i.e.,everycopyofaviralRNA

comprising 10000 nucleotideswillincludeonaverageonemutation.The

consequenceofthisisthat,giventhehighrateofviralreplication,allof

thepossibleviablemutantsofaviralspecieswilloccurandexisttogether

inaninhomogeneouspopulationknownasquasispecies.Theselectivepres-

sure(e.g.,hostimmunesystemefficiency)willacttoselectthe“fittest”

virusesatanygiventime.Thisexplainsthehighlevelofvariabilityseen

inHIVaswellasthephenomenonthatasinglepassageoftheattenuated

poliovaccinevirusthroughahumanvaccinerecipientproducesneuroviru-

lentrevertants.

Occurrenceof“new”viralspecies.Itappearstobetheexceptionratherthan

therulethataharmlessorsolelyzoopathicvirusmutatestobecomeanag-

gressivehumanpathogen.Infarmorecases,changedenvironmentalcondi-

tionsareresponsiblefornewformsofadisease,sincemost“new”virusesare

actually“old”virusesthathadreachedanecologicalbalancewiththeirhosts

andthenenterednewtransmissioncyclesasaresultofurbanization,migra-

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Kayser, Medical Microbiology © 2005 Thieme