Enterovirus.docx

Enterovirus.docx

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Enterovirus

EnterovirusesSlideSet

Enteroviruses

Theenterovirusesareagenusofthefamilypicornaviridae.Over70serotypesofenterovirushavebeenisolatedfromman.TheirnormalsiteofreplicationistheGItract,wheretheinfectioncanbesubclinicalorresultinamildGIdisorder.However,inaproportionofcases,thevirusspreadstootherorgans,causingseverediseasewhicharetypicalofindividualenterovirustypes.Thehumanenterovirusesincludethepolioviruses,coxsackieviruses,enterocytopathichumanorphan（ECHO）virusesandenteroviruses68-71.

Properties

ssRNA,nakedviruswithicosahedralsymmetry 

virion27nmindiameter 

stabletoacidpH,unlikerhinoviruses,andresistanttolipidsolventssincethereisnoenvelope 

capsidhas60copieseachof4proteins,VP1,VP2,VP3andVP4arrangedwithicosahedralsymmetryaroundagenomeofmessengersense.VP1formstheapiceswhilstVP2andVP3formtheface,VP4isinternal. 

asmallprotein,VPgiscovalentlylinkedtotheRNAatthe5'endoftheRNAgenome 

atleast72serotypesareknown 

thevirus-neutralizingepitopesresidemainlyinVP1,althoughtheactualsitesmaycoverVP2and/orVP3

ThegenomeofthevirusconsistsofassRNAmoleculeofpositivesense.Theviralproteinsaresynthesizedasonelargeproteinfromasingleopenreadingframe.Thelargeprecursorproteinincludes2knownsequencesthatactasproteolyticenzymesanddigesttheprecursorproteinatspecificsitesintoindividualproteins.Thefirst,P2A,cleavesthestructuralfromthenon-structuralproteins.Thesecond,P2B,completestheotherprocessingoftheprotein.（NBVP0istheprecursorofVP2andVP4andthefinalmaturationcleavagedonottakeplaceuntilassembly,wheretheactualcleavageisanautocatalyticprocess.）Thegenomicsequencesbetweenthevariousenterovirusesnowsequencedarewellconservedbetweenindividualmembersandalsowithrhinoviruses.Theexceptionisenterovirus72（hepatitisA）,whoseclassificationasanenterovirusisequivocalespeciallysinceitsmainsiteofreplicationisintheliver. 

Enterovirusparticles.（CourtesyofLindaM.Stannard,UniversityofCapeTown）

Classification

Theenterovirusserotypesofmanaredistinguishedonthebasisoftheirhomotypicseroneutralizationandexhibitawiderangeofbiologicalandpathogenicpropertieswhichareoftencharacteristicofindividualenterovirusserotypes.Thevirusesaredividedinto5groups,ie.polio,coxsackieA,coxsackieB,echo,andnewenterovirustypes.Polioviruswasfirstidentifiedin1909byinoculationofspecimensintomonkeys.Theviruswasfirstgrownincellculturesin1949.In1948,anewgroupofagentsbyinoculationintonewbornmicefromtwochildrenwithparalyticdisease.TheseagentswerenamedcoxsackievirusesafterthetowninNewYorkState.CoxsackievirusesAandBwereidentifiedonthebasisofthehistopathologicalchangestheyproducedinNewbornmiceandtheircapacitytogrowincellcultures.Laterathirdgroup,theechoviruses,wasidentifiedwhichproducedcytopathicchangesincellcultureandwasnonpathogenicfornewbornmiceandsubhumanprimates.Morerecently,newenterovirustypeshavebeenallocatedsequentialnumbers（68-71） 

GroupVirus

types

Monkey 

kidney

Humancell

culture

Pathologyin

newbornmice 

Majordiseaseassociations

Poliovirus 

3types

（1-3） 

+ 

+ 

- 

Paralyticpoliomyelitis,aseptic

meningitis,febrileillness. 

Coxsackie  

groupA

23types

（A1-22,A24） 

-orE 

-orE 

+  

Asepticmeningitis,herpangina,

febrileillness,conjunctivitis, 

hand,footandmouthdisease. 

Coxsackie

 groupB

 6types

（B1-6）

+

+

+

Asepticmeningitis,severeneonatal

disease,myopericarditis,Bornholm

disease,encephalitis,febrileillness

Echovirus  

31types 

（1-9,11-27）

+ 

E 

-  

Asepticmeningitis,rash,febrile 

illness,conjunctivitis,severe

generalizedneonataldisease. 

Enterovirus 

4types 

（68-71） 

+

+

-

Polio-likeillness,aseptic

meningitis,hand,footandmouth 

（E71）,epidemicconjunctivitis（E70）

Enterovirusesgainsentryintothebodythroughthealimentarytract.Viralreplicationtakesplaceinthecellsliningthealimentarytractandmaybeprecededoraccompaniedbyoropharyngealreplication.Forseveralenteroviruses,aviraemicphaseisfollowedbyinvolvementoftargetorganse.g.thespinalcord,brain,meninges,myocardiumorskin.Incubationperiodsvarywidelyfrom2to40days.Itisalsopossiblethatenterovirusescanbetransmittedbytherespiratoryroute,althoughitisnotknownhowmanytypescanbetransmittedthisway.Enterovirusescanprobablybetransmittedinthesamewayasothervirusescausingthecommoncold-thatisbyhandcontactwithsecretionsandautoinoculationintothemouth,nose,oreyes.Enterovirusinfectionsarerarelyassociatedwiththeconsumptionofcontaminatedwaterandfoods.

Poliomyelitis

Thereare3serotypesofpolioviruswithnocommonpoliovirusantigen.Theyhaveidenticalphysicalpropertiesandtheirbasesequencesshare36-52%homology.Humansaretheonlynaturalhostsforpolioviruses,OldWorldmonkeysandchimpanzeesaresusceptibletoinfection.Antigenicvariantsoftypes1and2havebeenreported,howevertheseantigenicdifferencesdonotaffectthecapacityofAbsinducedbyonestraintoprotectagainstotherstrainsofthesametype.Despitetheseminorintratypicdifferences,poliovirusesshowmarkedantigenicstability.Itisimportanttonotethatotherenterovirusesareoccasionallyassociatedwithapolio-likeillness,inparticularCoxsackievirusA7andenterovirus71.

A.Epidemiology

Poliovirusesaredisseminatedglobally.Indenselypopulateddevelopingcountries,almost100%ofthepopulationhaveAbstoall3typesofthevirusbefore5yearsofage.Epidemicsdonotoccurandparalyticdiseaseisrareastheincidenceofparalyticpoliomyelitisincreaseswithage,especiallyafter15yearsofage.Incountrieswithimprovedsanitation,infectionisoftendelayeduntiladulthoodwithaconsequentincreaseinthenumberofcasesofparalyticpoliomyelitis.Withtheadventofimmunization,poliomyelitisisonthevergeoferadicationinmanycountries.Poliomyelitisoccursprimarilyinthesummer,likethecommondiarrhoealdiseases.Thepatientismaximallycontagiousduringthefirstweekofillness,whenthevirusisexcretedbothinthepharynxandfaeces,buttheviruscontinuestobeexcretedinthefaecesforto5to17weeksaftertheonsetofillness.

B. ClinicalFeatures

Theincubationperiodisusually7-14days（range3-35days）.Followingingestion,thevirusmultipliesintheoropharyngealandintestinalmucosa.Thelymphaticsystem,inparticularthetonsilsandthePeyer'spatchesoftheileumareinvadedandthevirusentersthebloodresultinginatransientviraemia.Inaminorityofcases,thevirusmayinvolvetheCNSfollowingdissemination.Thefollowingarethepossibleoutcomesfollowingpoliovirusinfection:

-

1.Subclinicalinfection（90-95%） -inapparentsubclinicalinfectionaccountforthevastmajorityofpoliovirusinfections.

2.Abortiveinfection（4-8%） -thisgroupofpatientsonlysuffertheminorillnesswhichcomprisesofinfluenza-likesymptomssuchasfever,malaise,drowsiness,headache,nausea,vomiting,constipationandsorethroat.Recoveryoccurswithinafewdaysandthediagnosiscanonlybemadebythelaboratory.Theminorillnessmaybeaccompaniedbyasepticmeningitiswhichissimilartothemeningitiscausedbyotherenterovirusesandusuallyresolvewithoutsequelaewithin2-10days.

3.Majorillness（1-2%） -themajorillnessmaypresent2-3daysfollowingtheminorillness.Inmostcasesthough,themajorillnessoccurwithoutevidenceofanyprecedingminorillness.Signsofasepticmeningitisarecommon.Involvementoftheanteriorhorncellsleadtoflaccidparalysis.Painfulmusclespasmsandincoordinationofnon-paralysedmusclesmayoccur.Involvementofthemedullamayleadtorespiratoryparalysisanddeath.Theparalysisusuallydevelopsoverseveraldaysandsomerecoverymaytakeplace.Anyeffectspersistingformorethan6monthsareuauallypermanent.

C.LaboratoryDiagnosis

1.Virusisolation -theCSFusuallyshowthechangestypicalforthatofviralmeningitiswithlymphocytosisandahighproteinlevel.However,poliovirusisrarelyrecoveredfromtheCSF,incontrasttocoxsackieandechoviruses.Poliovirusisreadilyisolatedfromthroatswabs,faeces,orrectalswabsbyinoculationintocellculture.TheCPEproducedcanbeneutralizedbytypespecificserawhichformsthebasisforidentification.Theisolatemaybefurthertypedbymolecularassays.

2.Serology -thisisnotwidelyusedasvirustissueculturetechniquesaresoefficient.Neutralizationtests,inwhichacuteandconvalescentseraaremixedwithknownconcentrationsoflaboratorystrainsofpoliovirusandthenabsorbedontomonolayersofcellcultures,arethemostefficientserologicaltestsystemavailable.Alternatively,CFTscanbeusedbutthesearemuchlessreliable.

D.Prevention

Nospecifictreatmentisavailableexceptsupportivemeasuresinparalyticpoliomyelitis.However,itispossibletopreventthediseasethroughactiveimmunization.Threemajordiscoverieswereresponsibleforthedevelopmentofsuccessfulvaccines:

（1）Protectionisrequiredagainstall3typesofpoliovirus,

（2）Polioviruswillreplicatereadilyincellculturesderivedfromnonnervoustissue,and（3）viraemiaisessentialforthepathogenesisofparalyticpoliomyelitissothatserumantibodiesshouldinterrupttheviraemia.Thereare2vaccinesavailable:

（1）theinactivatedSalkvaccine,and

（2）theattenuatedSabinvaccine.

1.InactivatedSalkV