Rotavirus - Wikipédia, A Enciclopédia Livre

07/11/2016
RotavirusWikipdia,aenciclopdialivre
Rotavirus
Origem:Wikipdia,aenciclopdialivre.
Rotavirus(emlatim:rota,roda,pelasuaforma)umgnerodevrus
deRNAbicatenriodafamliaReoviridae.umasdasprincipais
causasdediarreiagraveemlactentesecrianasjovens,eumdo
diversosvrusquecausaminfeescomummentechamadasde
gastroenterite.Estimaseque,aoscincoanosdeidade,quasetodasas
crianasdomundotenhamsidoinfectadaspelorotavruspelomenos
umavez.Noentanto,comoemcadainfecoaimunidadese
desenvolve,asinfecessubsequentessomenosgraveseadultos
raramentesoafectados.Existemoitoespciesdestetipodevrus,
conhecidascomoA,B,C,D,E,F,GeH.ORotavrusA,omais
comum,oresponsvelpormaisde90%dasinfecesemseres
humanos.
Ovrustransmitidopelarotafecaloral.Infectaedanificaasclulas
querevestemointestinodelgado(entercitos)provocando
gastroenterite.Orotavrusfoidescobertoem1973eresponsvelpor
50%dosinternamentoshospitalaresdevidoadiarreiasagudasem
crianas.Paraalmdoseuimpactonasadehumana,osrotavrus
tambmcausaminfecesemanimais,inclusivenogado.
Causamgastroenteriteslimitadascomdiarreia,vmitos,muitador
abdominalenuseas,apstransmissoemcomida,objectosougua
infectadacomvrusprovenientedefezes.acausamaiscomumde
diarreiainfecciosanascrianasdaEuropa.
Ainfecoderotavrusgeralmenteumadoenafcildecontrolarna
infncia,noentanto,aindaassim,acadaanoemtodoomundo
morremcercade450milcrianascomidadesinferioresacincoanos
infectadas,amaioriadasquaisvivemempasesemviasde
desenvolvimentoeconmico,equasedoismilhesficamgravemente
doentes.Otratamentofeitopelaadministraodemuitaguacom
umpoucodesaleacar(sorocaseiro),pararestabeleceroslquidos
eelectrlitosperdidosnadiarreia.Ascampanhasdehigienepara
combaterosrotavruscentramsenaterapiadereidrataooralpara
crianasinfectadasenavacinaoparaprevenodadoena.A
incidnciaegravidadedasinfecesdorotavrusbaixou
significativamentenospasesqueincluramavacinaocontraos
rotavrusssuasnormasrotineirasdeimunizaodascrianas.
Rotavirus
Reconstruoporcomputadordumrotavrus
baseadaemvriasmicrografias
electrnicas.Umapartculadestevrus
esfricacomprotrusessuperficiais
regularmenteespaadas.
Classificaocientfica
Grupo:
GrupoIII(dsRNA)
Ordem:
Noatribudo
Famlia:
Reoviridae
Subfamlia: Sedoreovirinae
Gnero:
Rotavirus
Espcietipo
RotavirusA
Espcies
RotavirusA
RotavirusB
RotavirusC
RotavirusD
RotavirusE
RotavirusF
RotavirusG
RotavirusHa
ndice
1 Sintomatologia
2 Transmisso
3 Mecanismosdainfeco
4 Diagnsticoedeteco
5 Tratamentoeprognstico
6 Epidemiologia
7 Preveno
https://pt.wikipedia.org/wiki/Rotavirus
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7 Preveno
8 Infeconoutrosanimais
9 Virologia
9.1 Tiposderotavrus
9.2 Estrutura
9.3 Protenas
9.3.1 Protenasestruturais
9.3.2 Protenasviraisnoestruturais
9.4 Replicao
10 Histria
11 Referncias
12 Vertambm
13 Ligaesexternas
Sintomatologia
Agastroenteriteproduzidapelorotavrusumadoenaquepodesertantolevecomograve,caracterizadapor
vmitos,diarreiaaquosaefebrebaixa.Afectasobretudoascrianas.Umavezqueumacrianainfectadapelo
vrus,existeumperododeincubaodeaproximadamentedoisdiasantesdeapareceremossintomas.[1]Estes
geralmentecomeamcomvmitosseguidosporquatroaoitodiasdediarreiaabundante.Adesidrataomais
comumeminfecesderotavrusdoquenamaioriadaquelascausadasporpatgenosbacterianos,eacausa
maiscomumdasmortesrelacionadasinfecodorotavrus.[2]
AsinfecesderotavrusApodemocorrerdurantetodaavida:aprimeiravezgeralmenteconstituisintomas,
masassucessivaspossveisinfecessonormalmentelevesouassintomticas,[3][4]umavezqueosistema
imunitrioprovidenciaalgumaproteocontraovrus.[5][6]Consequentemente,asinfecessintomticasso
maisfrequentesemcrianascomidadesinferioresadoisanosedecresceprogressivamenteataos45anos.[7]
Ainfeconascrianasrecmnascidascomum,masgeralmenteestassociadaadoenaassintomticaou
leve[8]amaioriadossintomasgravestendemaocorreremcrianasentreosseismeseseosdoisanosdeidade,
ouentreidososepessoasimunodeprimidas.Devidoimunidadeadquiridaduranteainfncia,amaioriados
adultosnoestosusceptveisaorotavruseasgastroenteritesquesurgememadultosgeralmenteapresentam
outrosagentesdiferentesdorotavrus,noentantoinfeesassintomticasnosadultospodempreservara
transmissodainfeonacomunidade.[9]
Transmisso
Orotavrustransmitidopelarotafecaloral,atravsdocontactocommoscontaminadas,superfciese
objectos,[10]epossivelmenteporviarespiratria.[11]Asfezesdeumapessoainfectadapodemcontermaisde
10biliesdepartculasinfecciosasporgrama[3]esotosomentenecessriasmenosdecempartculaspara
transmitirainfecoaoutrapessoa.[8]
Osrotavrussoestveisnomeioambienteeforamencontradosemamostrasemesturiosanveisto
elevadoscomo15partculasinfecciosasporgaloamericano(3,78litros)ovruspermaneceinfecciosoentre
9e19dias.[12]Asmedidassanitriasadequadasparaaeliminaodebacteriaseparasitasparecemser
ineficazesnocontroledorotavrus,umavezqueaincidnciadeinfeesempasescomaltospadresdesade
similardospasesdenvelinferior.[11]
Mecanismosdainfeco
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Adiarreiacausadapordiversasactividadesdosvrus.Amabsoro
devesedestruiodasclulasdoepitliointestinaldenominadas
entercitos.AprotenatxicaNSP4dorotavrusinduzumasecreode
cloretodependentedoioclcioedaidade,queinterrompeo
transportadorSGLT1oqualintervmnareabsorodegua,reduzindo
aparentementeaactividadedasdissacaridasese,possivelmente,activa
osreflexossecretoresdependentesdoioclciodosistemanervoso
entrico.[13]Osentercitosintactossegregamlactasenointestino
delgadoaintolerncialactosedoleitecausadaporumadeficinciade
lactase,umsintomadainfecoderotavirus,[14]quepodepersistir
durantesemanas.[15]Muitasvezesadiarreiareaparecequandose
reintroduzoleitenadietadacriana,devidofermentaobacteriana
doaucardissacridolactosenointestino.[16]
Diagnsticoedeteco
Micrografiaelectrnicadeum
entercitoinfectadoporumrotavrus
comasuasuperfciedestruda
(acima)comparadocomumaclula
noinfectada(abaixo).Barrade
aproximadamente500nm.
Odiagnsticodasinfeesdorotavrusnormalmentefeitodepoisque
sediagnosticagastroenteritecomocausadumadiarreiagrave.
maioriadascrianasinternadasnoshospitaiscomgastroenteritelhes
feitoumexameparadetecodorotavrusA.[17][18]Odiagnstico
especficodainfecodorotavrusArealizadoexaminandoasfezesdascrianaspormeiodeumensaiode
imunoabsoroenzimtica.Ostestessosensveiseespecficosedetectamtodososserotiposdorotavrus
A.[19]Emlaboratriosdeinvestigaopodemserutilizadosoutrosmtodos,comoamicroscopiaelectrnicae
aPCR.[20]APCRcomreversotranscrio(RTPCR)podedetectareidentificartodasasespcieseserotiposde
rotavrusnoshumanos.[21]
Tratamentoeprognstico
Otratamentodasinfeesagudasderotavrusnoespecficoeimplicaotratamentodossintomase,omais
importante,amanutenodahidratao.[22]Senofortratado,ascrianaspodemmorrerdumagrave
desidrataodelaresultante.[23]Dependendodagravidadedadiarreia,otratamentoconsistenumaterapiade
reidrataooral,duranteaqualdadacrianaguaextraparabeberquecontmpequenasquantidadesdesais
eaucares.[24]Em2004,aOMSeaUNICEFrecomendaramousodesoluesdereidrataooraldebaixa
osmolaridadeesuplementosdezincoparatratamentoemduasfasesdadiarreiaaguda.[25]Algumasinfees
sogravesobastantequejustificamhospitalizao,duranteaqualseadministramfludosporviaintravenosa
ouportubonasogstrico,epodemsermonitorizadososnveisdeelectrlitoseglicemiadacriana.[17]As
infeesderotavrusraramentecausamoutrascomplicaes,eseacrianareceberotratamentoadequadoo
prognsticopositivo.[26]
Epidemiologia
OrotavrusAresponsvelpormaisde90%dasgastroenteritesporrotavrusnoshumanos,[27]eendmico
emtodoomundo.Acadaanoosrotavrusprovocammilhesdecasosdediarreianospasesemviasde
desenvolvimento,quase2milhesnecessitamdehospitalizaoeestimasequehaja453milmortesde
crianasmenoresdecincoanosdevidoaestadoena,[28][29]85%dasquaisvivemempasesno
desenvolvidos.[30][31][32]Oimportantepapeldorotavrusenquantocausadordediarreiasnosuficientemente
reconhecidopelacomunidadesanitriaemtodoomundo,[33]especialmentenospasesemviasde
desenvolvimento.[28]possvelafirmarquepraticamentetodasascrianasforaminfectadaspelorotavrus
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Variaoestacionaldasinfeesde
rotavrusAnumaregioda
Inglaterra:afrequnciadasinfees
aumentaduranteoinvernodo
hemisfrionorte.
antesdos5anos.[34]Entreascrianaspequenasaprincipalcausade
diarreiagrave,eresponsvelporaproximadamente20%doscasos,e
50%dashospitalizaesnestafaixaetria.[28]Osrotavruscausam37%
dasmortesatribudasatodosostiposdediarreiae5%detodasas
mortesinfantisemcrianascomidadesinferioresa5anos.[29][35][36]
Asinfeesporrotavrusdoseprincipalmenteduranteosmesesfrios
esecos.[37][38]Desconheceseonmerodecasosemquesepode
atribuiracomidacontaminada.[39]NoutraestimativafeitapelaUNICEF
eOMSindicadooseguinte:"Estimasequeorotavruscausa40%de
todososingressoshospitalaresdevidoadiarreiasentreoscrianas
abaixodos5anosdeidadeemtodoomundo,dandoorigema100
milhesdeepisdiosdediarreiaagudatodososanos,quetmcomo
resultadoamortedeentre350.000e600.000crianas".[40]
OssurtosdediarreiaprovocadaporrotavrusAsocomunsentreascrianaspequenashospitalizadas,as
crianasmaioresquefrequentamcreches,eidososemresidnciasdaterceiraidade.[41][42]Em2005omaior
registodeepidemiadediarreiaporrotavrusocorreuemNicargua,associadaamutaesnogenomado
rotavrusA,quepossivelmentefizeramcomqueovrusevitassedaimunidadeprevalentedapopulao.[43][44]
OrotavrusB,tambmchamadorotavrusdadiarreianosadultosouADRV,causougrandesepidemiasna
Chinaqueafectarammilharesdepessoasdetodasasidades.Essasepidemiasocorreramcomoresultadoda
contaminaodeguaspotveiscomguasresiduais.[45][46]TambmhouveinfeesderotavrusBnandia
em1998porumacepachamadaCAL,que,diferentementedoADRV,endmica.[47][48]Atagora,as
epidemiascausadaspelorotavrusBestoconfinadasfundamentalmenteChina.[49]
OrotavrusCfoiassociadoacasosraroseespordicosdediarreiaemcrianas,podendoafectaratodaa
famlia.[50]
Preveno
Comoamelhoriadasmedidashiginicasnodiminuiaprevalnciadas
doenasretrovirais,eafrequnciadehospitalizaessemantmalta
apesardousodeterapiadereidrataooral,aprincipalinterveno
sanitriaquesepodeaplicaravacinao.[51]Foramelaboradasduas
vacinascontraasinfeesderotavrusAquesoseguraseefectivasem
crianas:[52]RotarixdaGlaxoSmithKline[53]eRotaTeqdaMerckcom
estruturaseesquemasposolgicosdiferentes.[54]Ambasso
administradasporviaoralecontmvrusatenuadosvivos.[52]Estas
vacinasforamestudadasdeumaformaextensa,incluindopases
Osrotavrustmumacaracterstica
europeus,antesdoseulanamento,evidenciandoumbomperfilde
formaarredondada.
eficciaesegurana.Em2009,aOMSrecomendouqueseincluise
umavacinacontraosrotavrusemtodososprogramasnacionaisde
imunizao.[55]Aincidnciaegravidadedasinfeesporrotavrusdiminuiusignificativamentenospasesque
aplicaramestarecomendao.[56][52]Porexemplo,noMxico,queem2006estavaentreosprimeirospasesdo
mundoemqueavacinaocontraorotavrusfoiintroduzida,astaxasdedoenasdiarreicascaramduranteo
episdioderotavrusde2009emmaisdo65%entreascrianascomidadesinferiores2anos.[57]Em
Nicargua,queem2006seconverteunoprimeiropasemviasdedesenvolvimentoaintroduziravacinado
rotavrus,asinfeesgravesderotavrusforamreduzidasem40%eoingressonoscuidadosintensivospara
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metade.[58]NosEstadosUnidosavacinaocontraosrotavrusdesde2006temreduzidoashospitalizaes
relacionadascomorotavrusem86%.Asvacinaspuderamtambmcontribuirparaaprevenodadoenaem
crianasnovacinadasaolimitaronmerodeinfeescirculantes.[59]
Existemlicenasdevacinascontraorotavrusemmaisde100pases,masapenas28pasesintroduziramnos
seusplanosdevacinaorotineirosavacinaocontraorotavrus.[60][61][62][63]Osensaiossobreaseguranae
eficciadasvacinasRotarixeRotaTeqnafricaesiaconcluramqueasvacinasreduziamdrasticamenteas
diarreiasgravesentrecrianasnospasesemviasdedesenvolvimento,nosquaisocorriamamaioriadasmortes
porrotavrus.[64]Em2012arevisoCochranede41ensaiosclnicosemqueparticiparam186.263pessoas
concluiuqueoRotarixeoRotaTeqsovacinasefectivas.[65]Estoaserdesenvolvidasoutrasvacinascontraos
rotavrus.[66]Apartirdesetembrode2013,avacinafoioferecidaatodasascrianasnoReinoUnidoentreos
doisetrsmesesdeidade.[67]NoestadoEspanholavacinaoporrotavrusnoconstituipartedoprograma
geraldevacinaonemestfinanciadapelasadepblica,masrecomendadapeloComitAssessorde
VacinasdaAssociaoEspanholadePediatriaepelaSociedadeEuropeiadeGastroenterologia,[68]Hepatologia
eNutrioPeditrica(ESPGHAN)epelaSociedadeEuropeiadeInfetolgiaPeditrica(ESPID)eOrganizao
MundialdaSade(OMS).EmPortugal,asvacinascontraorotavrussocomercializadasdesde2006.Os
estudosrealizadosnoutrospasesdemonstramqueosbenefciosdavacinaocompensamoscustos,masat
quearelaocustoeficciaemPortugalsejaapurada,aSPPnotembaseparadefenderainclusonoPlano
NacionaldeSade.
AsrecomendaesamericanasdoAdvisoryCommitteeonImmunizationPractices(ACIP)de2009referemque
aadministraonodeveserfeitanohospitalpeloriscodetransmissodovrusvacinal.[69]Asrecomendaes
europeiasde2015daEuropeanSocietyforPaediatricInfectiousDiseases(ESPID)[70]defendemasua
utilizaonosaindahospitalizados,reforandoquenestascircunstnciasdeveroserrigorosamentecumpridas
asmedidasparaevitartransmissoagruposderisco.Umapublicaode2014sobreseguranadautilizaoda
vacinacontraorotavrusnumaunidadedecuidadosintensivosneonataisamericana,concluiuqueavacinaera
bemtoleradaecombaixoriscodetransmissosintomticaaosnovacinados.[71]
Apesardaslimitaesdosestudospelopequenonmerodedoentesincludos,osresultadossugeremqueas
crianasinfetadasporVIHtmumarespostaaestavacinacomparvelscrianasVIHnegativassendoambas
bemtoleradas.[72][73]
AorganizaonogovernamentalPATH,aOMS,osCentersforDiseaseControlandPreventiondeEEUU,ea
GAVIAllianceestoatrabalharparalevarasvacinasderotavrusaospasesemviasdedesenvolvimento,onde
seoriginamamaioriadoscasosemortesemcrianas.[74]
Infeconoutrosanimais
Osrotavirusinfetamcriasdemuitasespciesdeanimaisesoumadasprincipaiscausasdediarreianos
animaisselvagensedomsticosemtodoomundo.[75]Comosoumagentepatognicodogado,
designadamentedebezerroseleites,orotavrusumadascausasdeperdaseconmicasdosagricultores
devidoaoscustosdostratamentosassociadoscomelevadosnveisdemorbilidadeemortalidade.[76]Estes
rotavrusqueafectamosanimaissoumpotencialreservatrioparaointercmbiogenticocomosrotavrusde
humanos.[76]Existemevidnciasdequeosrotavrusanimaispodeminfetarhumanos,querportransmisso
directadovrusquerporcederumouvriosdosseussegmentosgenmicosdeRNAacepashumanas(por
redistribuioourecombinao).[77][78]
Virologia
Tiposderotavrus
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Existemcincoespciesderotavrus,denominadasA,B,C,DeE.Asinfeesemhumanosdevemse
principalmentesespciesA,BeC,masespecialmenteA.Ascincoespciespodemprovocardoenas
noutrosanimais.[79]OrotavrusAtemvriascepas,chamadasserotipos.[80]Paraosrotavrus,similarmenteao
queocorrenovirusdagripe,utilizadoumsistemadeclassificaodualbaseadonasduasprotenasde
superfciedovrus.UmadelasaglicoprotenaVP7,quedefineosserotiposG,eaoutraaprotenaVP4
sensvelprotease,quedefineosserotiposP.[81]UmavezquedoisgenesquedeterminamostiposGeP
podemtransmitirseseparadamenteprogniedestesvrus,soencontradasdiferentescombinaes.[82]
Estrutura
Ogenomadorotavrusconsistede11molculasdeRNAbicatenriodistintas,quepossuemumtotalde18.555
nucletidos.Cadaumdestessegmentosoumolculasumgene,numeradosdo1ao11portamanho
decrescente.Cadagenecodificaumaprotena,exceptoogene9,quecodificaduas.[83]ORNArodeadopor
umacpsideproteicaicosadricadetrscamadas.Aspartculasviraistmcercade76,5nmdedimetroeno
apresentamenvoltura.[84][85]
Protenas
Existemseisprotenasvirais(VPs),queformamapartculavrica(virio).Estasprotenas
estruturaisdenominamseporVP1,VP2,VP3,VP4,VP6eVP7.ParaalmdasVPs,existemseisprotenas
noestruturais(NSPs),queseproduzemsnasclulasinfectadasporrotavrus,designadamente:NSP1,
NSP2,NSP3,NSP4,NSP5eNSP6.[79]
Pelomenosseisdasdozeprotenascodificadaspelogenomado
rotavrusunemseaoRNA.[86]Afunodestasprotenasnareplicao
dorotavrusnototalmentecompreendidaacreditasequeestejam
relacionadascomasntesedeRNAeoseuempacotamentonovirio,o
transportedeRNAmparaostiodereplicaodogenoma,eatraduo
doRNAmeregulaodaexpressogentica.[87]
Protenasestruturais
AVP1estlocalizadanapartecentral(ncleo)dovruseumaenzima
RNApolimerase.[88]Numaclulainfectadaestaenzimaproduz
transcriesdeRNAmparaasntesedeprotenasviraiseproduzcpias
dossegmentosdeARNqueformamogenomadorotavrusparaa
produodenovaspartculasvricas.
AVP2formaacamadacentraldovirioeligaseaogenomade
RNA.[89]
Diagramasimplificadodalocalizao
deprotenasestruturaisderotavrus.
Aimagemmostraasmolculasde
RNArodeadaspelaprotenaVP6que
estrodeadapelaprotenaVP7.A
protenaV4destacasedasuperficie
dapartculavricaesfrica.
AVP3formapartedoncleointernodovirioeumaenzimachamada
guanililtransferase,quecatalizaaformaodacap5'duranteamodificaopstranscricionaldoRNAm.[90]
Acap5'estabilizaoRNAmviralaoprotegelodasenzimasquedegradamoscidosnucleicosdesignadosde
nucleases.[91]
AVP4estnasuperfciedovirioesobressaicomoumaespcula.[92]Ligaseamolculasreceptorasda
superfciecelulareorientaaentradadovrusnaclula.[93]AVP4devesermodificadapelaenzimatripsina
(umaprotease),queseencontranotratodigestivo,transformandoseemVP5*eVP8*antesqueovruspossa
tornarseinfeccioso.[94]AVP4determinaoquovirulentoovirusedefineotipoPdovrus.[95]
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AVP6formaamassadacpside.fortementeantignicaepodeser
utilizadaparaidentificarasespciesderotavrus.[3]Estaprotena
utilizadaemtesteslaboratoriaisparaasinfeesderotavrusA.[96]
AVP7umaglicoprotenaqueformaasuperfcieexternadovirio.
Paraalmdassuasfunesestruturais,determinaqueovirussejauma
cepadotipoGe,juntamentecomaVP4,estimplicadanaimunidade
infeco.[84]
Protenasviraisnoestruturais
ANSP1,produtodogene5,tratasedumaprotenanoestruturalque
seuneaoRNA.[97]
ANSP2umaprotenadeligaoaoRNAqueseacumulanas
inclusescitoplasmticas(viroplasma)necessriaparaareplicaodo
genoma.[98][99]
ANSP3ligaseaoRNAmviralnasclulasinfectadaseresponsvel
pelobloqueiodasntesedeprotenascelulares.[100]
ANSP4umaenterotoxinaviralqueinduzdiarreiaefoiaprimeira
enterotoxinaviraldescoberta.[13]
Micrografiaelectrnicade
nanopartculasdeouroligadasaum
rotavrus.Osobjectoscirculares
pequenosescurossonanopartculas
deourocobertascomumanticorpo
monoclonalespecficoparaaprotena
VP6dorotavrus.
ANSP5codificadapelosegmentogenmico11dorotavrusAeemclulasinfectadaspelovrusaNSP5
acumulasenoviroplasma.[101]
ANSP6umaprotenaqueseligaacidosnucleicos,[102]ecodificadanogene11apartirdumquadrode
leituraabertaforadefase.[103]
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Segmento
deRNA
(gene)
Tamanho
(paresde
bases)
3302
Protenasegenesderotavrus
Peso
Cpias
Protena molecular Localizao
por
(kDa)
partcula
VP1
Funo
125
Nosvrticesda
partecentral
('ncleo')
<25
RNApolimeraseRNA
dependente
120
EstimulaaRANreplicaseviral
2690
VP2
102
Formaacamada
internado
ncleo
2591
VP3
88
Nosvrticesdo
ncleo
<25
Enzimaguanililtransferaseque
colocaacap5'noRNAm
2362
VP4
87
Espculade
superficie
120
Ligaoclula,virulncia
1611
NSP1
59
Noestrutural
Ligaoextremidade5'do
RNA
1356
VP6
45
Cpsidainterna
780
Estruturaleantgenoespecfico
deespcie
1104
NSP3
37
Noestrutural
Aumentaaactividadedo
RNAmviraledetmasntese
proteicacelular
1059
NSP2
35
Nonestrutural
NTPaseenvolvidano
empacotamentodoRNA
1062
VP7
VP7
38e34
Superfcie
780
Estruturaleantgenode
neutralizao
10
751
NSP4
20
Noestrutural
Enterotoxina
667
NSP5
NSP6
ModuladorqueseligaaoRNA
monocatenrioebicatenriode
NSP2
11
22
Noestrutural
EstatabelabaseadanoestudodacepadorotavrussmioSA11.[104][105][106]Asatribuiesdecodificaoda
RNAprotenadiferemnalgumascepas.
Replicao
Osrotavirusreplicamseprincipalmentenotratogastrointestinal,[107]e
infectamosentercitosdasvilosidades(villi)dointestinodelgado,
provocandomudanasestruturaisefuncionaisnoepitlio.[108]Otriplo
recobrimentoproteicodovrustornaoresistenteaopHcidodo
estmagoesenzimasdigestivasdotratogastrointestinal.
Ovrusentranasclulasporendocitosemediadaporreceptoreseforma
umavesculachamadaendossoma.Asprotenasdaterceiracamada(a
VP7eaespculaVP4)rompemamembranadoendossoma,criando
umadiferenanaconcentraodoclcio.Istoprovocaaroturados
trmerosdaVP7emsubunidadesproteicasseparadas,deixandoasVP2
eVP6envoltadoARNbicatenrioviral,formandoumapartculade
Representaosimplificadadociclo
dereplicaodumrotavrus.
duplacamada(DLP).[109]
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07/11/2016
AsonzemolculasdeARNbicatenriopermanecemdentrodasduascamadasproteicasprotectoraseaRNA
polimeraseDNAdependenteviralgeratranscritosdeRNAmdogenomaviralbicatenrio.Aopermanecer
dentrodoncleo,oRNAviralconsegueevadirasrespostasimunitriasdohspedequeutilizamoRNAde
interferncia,quesoativadaspelapresenadoRNAbicatenrionaclula.
Duranteainfeco,orotavrusproduzARNmtantoparaasntesedeprotenascomoparaareplicaognica.
Amaioriadasprotenasdorotavirusacumulamsenoviroplasma,ondesereplicaoRNAeseaglomeramas
partculasdeduplacamada(DLPs).Oviroplasmafarmaseaoredordoncleocelularapenasduashorasdepois
dainfecovrica,econsistedefbricasviraisquesepensaseremformadasporduasprotenasvricasno
estruturais:NSP5eNSP2.AinibiodaNSP5porinterfernciadeRNAdlugaraumafortediminuiona
replicaodosrotavrus.Aspartculasdeduplacamadamigramparaoretculoendoplasmtico,ondeadquirem
asuaterceiracamada,amaisexterna(formadaporVP7eVP4).Osvrusfilhosliberamsedaclulapor
lise.[94][110][111]
Histria
Em1943,JacobLuzeHoraceHodesprovaramqueumagentefiltrvel
nasfezesdecrianascomdiarreiainfecciosa,tambmcausoudiarreia
(diarreiadosanimais)embovinos.[112]Trsdcadasmaistarde,
amostrasconservadasdoagentemostraramsecontraorotavrus.[113]
Nosanosseguintes,umvrusemcamundongosmostrouserelacionado
comovrusquecausadiarreia.[114][115]Em1973,RuthBishop
descreveuvrusrelacionadosencontradosemcrianascom
gastroenterite.[116][117]
Em1974,ThomasHenryFlewettsugeriuonomederotavrusdepoisde
observarque,quandovistoatravsdeummicroscpiodeeltrons,uma
partculaderotavruspareceumaroda(rota,emlatim)[118][119]onome
Diagramasimplificadodalocalizao
dasprotenasestruturaisdorotavrus.
foioficialmentereconhecidopeloComitInternacionaldeTaxonomia
deVrusquatroanosdepois.[120]Em1976,osvrusrelacionadosforamdescritosemdiversasoutrasespcies
deanimais.[115]Essesvrus,todoscausandogastroenteriteaguda,foramreconhecidoscomoumpatgeno
coletivoqueafetasereshumanoseanimaisemtodoomundo.[118]Sorotiposderotavrusforamprimeiramente
descritosem1980,[121]enoanoseguinte,orotavrusapartirdesereshumanosfoicultivadoemculturasde
clulasderivadasderinsdemacaco,pelaadiodetripsina(umaenzimaencontradanoduodenodemamferos
eagoraconhecidaporseressencialpararotavrusparareplicar)aomeiodecultura.[122]Acapacidadede
cultivarrotavrusemmeioculturafoiresponsvelporaceleraroritmodasinvestigaes,e,emmeadosda
dcadade1980osprimeiroscandidatosavacinasestavamsendoavaliados.[123]
Em1998,umavacinacontraorotavrusfoilicenciadaparausonosEstadosUnidos.Ensaiosclnicosnos
EstadosUnidos,FinlndiaeVenezuelahaviamencontradoentre80e100%deeficincianaprevenode
diarriagravecausadaporrotavrus,eosinvestigadoresnotinhamdetectadonenhumefeitoadversograve
estatisticamentesignificante.[124][125]Ofabricante,porm,retiroudomercadoem1999,depoisquese
descobriuqueavacinapodetercontribudoparaumaumentodoriscodeintussuscepo,umtipodeobstruo
intestinal,emumadecada12.000crianasvacinadas.[126]Aexperinciaprovocouumintensodebatesobreos
riscosebenefciosrelativosdeumavacinacontraorotavrus.[127]Em2006,duasnovasvacinascontraa
infecodorotavrusforammostradasseguraseeficazesemcrianas,[128]e,emjunhode2009,aOrganizao
MundialdeSaderecomendaqueavacinaocontraorotavrussejaincludaemtodososprogramasnacionais
deimunizaoparafornecerproteocontraestevrus.[129]
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07/11/2016
Em2015,andiarevelouumavacinamaisbaratacomoapoiodoInstitutoNacionaldeSadedosEstados
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