Medical Microbiology

458 8 VirusesasHumanPathogen

Orthomyxoviruses

&TherepresentativesofthisfamilyarethedifferentinfluenzaAviruses.The

Atypeisthemostimportantofthethree.Itisthepathogenresponsiblefor

epidemicsandpandemics,sinceitsantigenicitystructurechangeswithina

narrowerrangeduetopointmutations(morefrequent)andwithinabroader

rangeduetorecombination(lessfrequent).TypeBtendstobeendemicand

typeCisveryrare.Influenzavirusesaretheclassicflupathogens,whereby

theclinicalpictureisoftencharacterizedbybacterialsuperinfectionsaswell.

Diagnosis:isolationincellcultures,serologylaterinthecourseofthein-

fection.

Prevention:deadvaccineforhigh-riskpersons,e.g.,withcirculatorydis-

eases. &

Pathogen.Thisfamilyhasonegenus,Influenzavirus,withthethreetypes

influenzaA,B,andC.InfluenzaAisbyfarthemostimportantandmostfre-

quentlyobservedinfluenzavirus.Itrepeatedlycausesepidemicsandeven

pandemicsatgreaterintervals,incontrasttoinfluenzaB,whichtendstoper-

sistinendemicformandcausesfewoutbreaks.InfluenzaCisrarelyisolated,

mostfrequentlyinyouths.Itplaysonaminorroleasaninfectivepathogen.

StructureandReplication

Allinfluenzavirusesshowthesamestructure(seeFig. 7. 3 ,p.380)andapro-

nouncedpleomorphism.Inhumantissuesandfreshisolates,somefilamentous

formsseveralmicrometerslongarefound,withincreasinglyroundformsdominat-

ingafterseverallaboratorypassages.Thegenomeoftheinfluenzavirusesisseg-

mentedandcompriseseightseparateantisenseRNAstrands,eachofwhichcodes

foronespecificprotein.Togetherwiththenucleoprotein,theyformthehelicalnu-

cleocapsid.CloselyassociationwiththisstructureistheRNApolymerasecomplex,

whichconsistsofthreehigh-molecular-weightproteinswithdifferentfunctions.

Thenucleocapsiditselfisembeddedinaprotein(so-calledmembraneormatrix

protein).Thevirusisenclosedbyanenvelopemadeofcellmembranelipids

withviralproteininclusions(hemagglutininandneuraminidase,responsiblefor

infectivityandviralprogenyrelease).Bothproteinsareseenundertheelectron

microscopeasprotrusions(“spikes”)onthevirussurface.

Replicationoftheinfluenzavirusesproceedsasdescribedonp. 385 fortheanti-

sense-strandviruses,wherebythecapoftheviralmRNAisacquiredbywayofa

uniquemechanism.First,aproteinofthepolymerasecomplexseparatesthe

cap,togetherwith 10 – 13 nucleotides,fromthecellularRNAmoleculesbycleavage.

Thisshort,cap-bearingsequenceservesastheprimerinthesynthesisofviral

mRNA,whichthereforebeginswithacellularcapandasmallpieceofcellular

RNA. "

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Kayser, Medical Microbiology © 2005 Thieme