8/11/2019 Alphavirus Mutator Variantes Defeitos Especficos Do Hospedeiro Presente e Atenuao Em Modelos de Mamferos

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Alphavirus Mutator Variantes Defeitos especficos dohospedeiro Presente e Atenuao em Modelos demamferos e insetos

Kathryn Rozen-Gagnon, 1, 2Kenneth A. Stapleford, 1Vanesa Mongelli, 3Herv Blanc, umaAnna-Bella

Failloux, 4Maria-Carla Saleh, 3eMarco Vignuzzi1, *

Laura D. Kramer, Editor

PLoS Pathog. Janeiro 2014; 10 (1): e1003877.

Publicado on line em 16 de Jan de 2014 doi:10.1371 / journal.ppat.1003877

Introduo

Durante a replicao, os vrus de RNA gerar cerca de 1 erro por 10 4nucleotdeos copiados,

dando origem a uma imensa populao de variantes geneticamente distintas, mas

intimamente relacionadas[1],[2],[3],[4]. A diversidade gentica destes enxames

"mutantes" no detectado pelo seqenciamento consenso, que, at data tem sido a base

para a maioria dos estudos de infeco viral. No entanto, essa falta de informaes sobre a

diversidade gentica tem obscurecido aspectos cruciais da biologia do vrus. Apesar de as

polimerases de ARN dependente de ARN (RdRp) tm uma elevada taxa de erro intrnseca, as

suas taxas de mutao pode ser modificado para gerar ambas as variantes de maior fidelidade

e inferiores (antimutators e mutantes, respectivamente),[5],[6],[7],[

8],[9],[10],[11],[12],[13],[14]. At o momento, variantes antimutator so pensados

para replicar de forma mais lenta, fazendo menos genomas com maior preciso; em contraste,

as variantes mutantes tm sido mostrados para replicar de forma mais rpida, mais a sntese

de genomas virais, mas a introduo de muitos erros durante o processo de replicao

de[8],[15],[16],[17],[18]. Apesar disso, o crescimento global e os ttulos de variantes de

fidelidade da polimerase no so significativamente diferentes, quando cultivada em

isolamento em cultura de clulas; para mutators os efeitos negativos da acumulao de

mutaes deletrias so apenas perceptvel aps vrias rodadas de replicao[6],[19]. Em

trabalhos recentes, essas variantes tm sido teis em explorar como o curso da infeco viral

afetado por qualquer uma diversidade restrita ou alargada populao[4],[10].

As evidncias atuais indicam que as freqncias de mutao de vrus de RNA foram

otimizados ao longo do tempo a ser nem muito precisas nem muito

errnea[4],[6],[16],[20],[21],[22],[23]. Pensa-se que a replicao propenso a erros

permite que o vrus para explorar o espao de sequncia para ganhar adaptabilidade e

acumulam mutaes potencialmente vantajosas. Durante vrios vrus de RNA, limitando a

diversidade da populao viral tem custos de fitness in vivo.Apesar de

semelhantes nafentipos de crescimento in vitro,as variantes que fazem menos erros

reduziram ttulos e exibem tropismo restrito em modelos animais[19],. Esta restrio no

tropismo pode ser devido a interaes inter-variantes cooperativas ou variantes minoritriasbenficos que esto faltando em uma situao com a diversidade da populao

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=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Vignuzzi1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Vignuzzi1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Loeb1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Holland3https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Holland2https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Holmes1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Furio2https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Gnadig1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Lauring1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Mansky1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Lauring1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Vignuzzi1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Gnadig1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Gong1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Weeks1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Furio2https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Furio1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Arnold1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Sadeghipour1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Suarez1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Drake2https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Speyer1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Mansky1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-FerrerOrta1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Arnold1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Arnold1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Graham1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Gnadig1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Pfeiffer1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Lauring1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Holland1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Drake1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Eigen1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://dx.doi.org/10.1371%252Fjournal.ppat.1003877&usg=ALkJrhg2qmgfIwFKIVGkRVWqlSvM6eiCAwhttps://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pubmed/%3Fterm%3DVignuzzi%2520M%255Bauth%255D&usg=ALkJrhijGo6aNRZqN_fNWCU-Rv90B8BjFQhttps://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pubmed/%3Fterm%3DSaleh%2520MC%255Bauth%255D&usg=ALkJrhix7BfhUyXZ_jY3J9PHtzxcTv_S0Qhttps://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pubmed/%3Fterm%3DFailloux%2520AB%255Bauth%255D&usg=ALkJrhj1IKzsdJIOEX5IdzLHiWvHgvDCzwhttps://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pubmed/%3Fterm%3DFailloux%2520AB%255Bauth%255D&usg=ALkJrhj1IKzsdJIOEX5IdzLHiWvHgvDCzwhttps://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pubmed/%3Fterm%3DBlanc%2520H%255Bauth%255D&usg=ALkJrhi9Tx9gx25M1pU6ct1UWgix-7PM5Qhttps://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pubmed/%3Fterm%3DMongelli%2520V%255Bauth%255D&usg=ALkJrhg820M2nhluMoTruNKM8MOuCoTGoghttps://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pubmed/%3Fterm%3DStapleford%2520KA%255Bauth%255D&usg=ALkJrhjfQYBSOaeekWqzRBMUBqXGEYg8tAhttps://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pubmed/%3Fterm%3DRozen-Gagnon%2520K%255Bauth%255D&usg=ALkJrhiR3P-LJoBeG2O1AifBYCxLo7w2yw

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restrito[19]. Prope-se tambm que as elevadas taxas de mutao da gripe A pode contribuir

para tropismo, permitindo a infeco de novos hospedeiros[26]. Portanto, parece que as

relativamente elevadas taxas de erro de vrus de ARN de gerar um nvel de diversidade que

facilita vantagens aptido adaptativos.

Em contraste, existe tambm um limite superior a frequncias de mutao; se cruzado, as

taxas de erro extremas levam acumulao de mutaes deletrias e perda de integridade

gentica. Prova disto demonstrado pelo tratamento de numerosos vrus de RNA com

agentes mutagnicos anlogos de nucleosdeos, que aumentam as frequncias de mutao e

resultar em extino por mutagnese letal[27],[28],[29],[30],[31]. Apesar de, at agora,

mutators RdRp no apresentam defeitos de crescimento em isolamento in vitro,um estudo

recente mostrou que mutantes e antimutator cepas de HIV eram menos aptos do que o tipo

selvagem em ensaios de competio[32]. Alm disso, vrios estudos recentemente

relatam naatenuao vivode cepas mutantes: cepas mutantes vrus Coxsackie B3 apresentam

reduzida ttulos virais em rgos-chave e no conseguem estabelecer infeces persistentes

em camundongos[6], e uma sndrome respiratria aguda grave (SARS) cepa mutante

coronavrus exposies reduzidas patognese em vrios modelos de mouse[7].

Antimutator e mutantes variantes so ferramentas valiosas para estudar onde existe o limite

de erro polimerase vantajoso para vrus que enfrentam presses seletivas diferentes. A este

respeito, representam uma posio arbovrus evolutiva especial devido sua necessidade de

se replicar em hospedeiros diferentes, que acompanhado por presses selectivas

distintas. Aptido arbovrus no necessariamente reduzido devido a obrigar host-ciclismo

(passagens de CHIKV alternada no limitou aptido viral), no entanto, tem sido demonstradoque evolvability pode ser reduzida devido a estas limitaes

evolutivas[33],[34],[35],[36],[37],[38]. Para alphavirus, as evidncias sugerem que a

diversidade viral mais restrito no inseto hospedeiro, devido a mais rigorosa gargalos

populacionais e presses seletivas[33],[34],[35],[37],[39],[40]. Desde variantes

minoritrias so pensados para jogar um papel importante na patognese arbovrus,

transmisso e emergncia[25],[41],[42],[43],[44],[45], as implicaes de fidelidade

polimerase alterada e taxas de mutao mrito estudo mais aprofundado. Recentemente, esta

questo foi parcialmente abordado usando uma variante do vrus chikungunya

antimutator[25].

Vrus Chikungunya (CHIKV) um arbovrus re-emergente, transmitida peloAedesespcies

de mosquitos. Este vrus de ARN de cadeia positiva

(famlia Togaviridae,gneroAlphavirus)tem um genoma de 11,8 kB, dos quais os primeiros

7,5 kb codifica quatro protenas no estruturais (nsP1-4) envolvidas em diversos processos,

incluindo a sntese de ARN, a evaso imune, e tropismo hospedeira[46

],[47],[48],[49],[50],[51],[52].Na maioria dos casos, as funes destas protenas so

putativo em CHIKV e s foram mostrados em modelos virais relacionados, tais como o vrus

da floresta de Semliki e vrus Sindbis[53],[54],[55],[56]. NSP4 a RdRp, responsvel

pela incorporao de nucletidos durante a replicao[57]. Anteriormente, foram isoladas de

https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Vignuzzi1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Vignuzzi1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Vignuzzi1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Schultz1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Schultz1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Vignuzzi2https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Vignuzzi2https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Vignuzzi2https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Anderson1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Anderson1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Anderson1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Bull1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Bull1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Bull1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Graci1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Graci1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Graci1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Dapp1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Dapp1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=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pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Ciota1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Ciota1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Ciota1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Greene1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Greene1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Greene1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Deardorff1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Deardorff1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Deardorff1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Coffey2https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Coffey2https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Coffey2https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Coffey3https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Coffey3https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Coffey3https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Coffey4https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Coffey4https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Coffey4https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Greene1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Greene1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Greene1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Forrester1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Forrester1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Forrester1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Weaver1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Weaver1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Weaver1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Coffey1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Coffey1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Ciota2https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Ciota2https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Ciota2https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Lin1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Lin1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Lin1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Jerzak1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Jerzak1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Jerzak1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Kurosu1https://translate.googleusercontent.com/translate_c?dep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ed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-SaxtonShaw1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Kim1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Kim1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Kim1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Tomar1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Tomar1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Tomar1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Tomar1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Kim1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-SaxtonShaw1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Lemm1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-MayuriGeders1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Solignat1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF8&prev=_t&rurl=translate.google.com.br&sl=en&tl=pt-BR&u=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894214/%3Ftool%3Dpubmed&usg=ALkJrhhO3KyGTlZZhYw0DYECbAHhmqjl2g#ppat.1003877-Schwartz1https://translate.googleusercontent.com/translate_c?depth=1&hl=pt-BR&ie=UTF