Medical Microbiology

SubviralPathogens:ViroidsandPrions 473

Prions

Pathogen.Attentionwasfirstdrawntocertainencephalopathicagents

whosephysicalpropertiesdifferedgreatlyfromthoseofviruses.Forinstance,

theyshowedveryhighlevelsofresistancetosterilizationandirradiationpro-

cedures.Itwaslaterdeterminedthatthesepathogens—incompletecontrast

tovirusesandviroids—requireonlyprotein,andnonucleicacid,asthebasis

oftheirinfectivityandpathogenicity.Thisgaverisetotheterm“prion”for

“proteinaceousinfectiousparticle.”Anintensivesearchfornucleicacidin

the“particles”wasfruitless.

Prionsaremisfoldedformsofacellularprotein.Theyconsistofonlya

singleprotein(PrP,prionprotein),whichnaturallyoccurs,forexample,on

thesurfaceofneurons.Theregioncoding forthis proteinofapprox.

35 kDaislocatedinasingleexonandisderivedfromacellulargeneex-

pressedinbothhealthyanddiseasedbrains.Disease-associatedPrP(the

best-knownprionisthescrapiepathogen,theproteinofwhichiscalledPrPsc

[scforscrapie]),isamutant,slightlyshortened(2 7 – 30 kDa)formofthe

normalPrPc(cforcell).ItdiffersfromnormalPrPcinitsalteredconfiguration,

itsnearlycompleteresistancetoproteasesandinthefactthatittendsto

accumulateinsidethecell.

Pathogenesis.InfectiousPrPsccantransformnaturallyoccurringPrPcinto

PrPsc,resultinginanautocatalyticchainreactioninwhichmainlythepatho-

logicalproteinisproduced.ThisiswhymicelackingthegeneforPrP(geneti-

callyengineered“knockoutmice”)cannotbeinfectedwiththepathological

PrPscprion.Depositsoflargeamountsofthepathologicalproteinintheform

ofso-calledamyloidplaquesarevisibleunderamicroscopeinbraintissue

frominfectedhumansandanimals.

Clinicalpicture.Thefollowingencephalopathiesareconsideredtobecaused

byprioninfections:

Inhumans:

&Creutzfeldt-Jakobdisease(CJD)

&NewvariantCJD(nvCJDorvCJD)

&Gerstmann-Stra ̈ussler-Scheinker(GSS)syndrome

&Kuru

Inanimals:

&Scrapie(sheep,goats)

&Transmissibleminkencephalopathy(TME)

&Wastingdisease(deer)

&Bovinespongiformencephalopathy(BSE,“madcowdisease”)

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Kayser, Medical Microbiology © 2005 Thieme