Medical Microbiology

RNAviruses 463

bytheAfricanLassaandtheSouthAmericanJuninandMachupoviruses

showhighlethalityrates(hemorrhagicfevers).

Diagnosis:Lassa:virusisolationinspeciallaboratories(biosafetylevel4).

LCM:serology. &

Pathogen.MostmembersoftheArenaviridaefamilywerefirstidentifiedin

the 1 960s.Theprotoypearenavirus,thepathogenthatcauseslymphocytic

choriomeningitis(LCM),wasidentified 30 yearsearlier.Studiesinvolving

thisvirushavecontributedagreatdealtoourunderstandingofcellularim-

munityingeneralandinfection-relatedimmunopathologyinparticular.

ThehumanpathogensamongthearenavirusesaretheLCMvirus(Europe,

America),theLassavirus(Africa),andtheJuninandMachupoviruses(South

America).Allarenavirusesaresphericaltopleomorphicand 50 – 300 nmin

size(onaverage 110 – 130 nm).Theyconsistofa“spiked”envelopederived

fromtheplasmamembrane,withaninnerstructurethatappearstobe

granulatedwhenviewedinultrathinsections.Itistothesegranulatheviral

familyowesitsname(arenosus=sandy).Theyareconsideredtobehost-cell

ribosomes.ThevirioncontainsatleastthreestrandsofhostRNAinaddition

totwoviralRNAsegments.

AmbisenseGenome

Thegenomeofthearenavirusescontainsgenomiccomponentswithsense(plus)

polarityandotherswithantisense(minus)polarity(ambisenseviruses,seep. 38 7)

andisstructuredasfollows:thesmallerSpart(S=small)codesinthe 30 partasan

antisense-strandRNAforthenucleocapsidprotein(NP)andinthe 50 partassense-

strandRNAforaviralglycoprotein.Eachproteinistranslatedseparatelyfromthe

subgenomicRNA;theNP,codedwiththeantisenseorientation,isfirsttranscribed

intoasense-strandRNA.TheLpart(l=large)codesatthe 30 endinantisense-strand

orientationfortheviralpolymeraseandatthe 50 endinsense-strandorientationfor

aregulatoryRNA-bindingprotein.

Pathogenesisandclinicalpicture.Thesourceofnearlyallhumanarenavirus

infectionsistobefoundinrodents.Thevirusentersthebodyperos,aero-

genicallyorpossiblyalsobyskincontact.Apronouncedviremiadevelopsat

first,followedbyorganmanifestations.InthecaseofLCMthesearenormally

harmlessandflulike,althoughtheycanalsodevelopintomeningitisoren-

cephalitis,inrarecaseswithalethaloutcome.TheLassavirusispantropic.It

causesahemorrhagicfeveraffectingnearlyallinnerorgansandhasahigh

rateoflethality.Deathresultsfromshockandanoxia.Theclinicalpicturere-

sultingfromJuninandMachupovirusinfectionsissimilar.ComparedtoLassa

infections,CNSinvolvementismorefrequentandthelethalityrateissome-

whatlowerwiththesetwoviruses.

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Kayser, Medical Microbiology © 2005 Thieme