On the entry of an emerging arbovirus into host cells: Mayaro virus takes the highway to the cytoplasm through fusion with early endosomes and caveolae-derived vesicles
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Digital do Instituto Evandro Chagas (Patuá) |
Texto Completo: | https://patua.iec.gov.br/handle/iec/2878 |
Resumo: | Mayaro virus (MAYV) is an emergent sylvatic alphavirus in South America, related to sporadic outbreaks of a chikungunya-like human febrile illness accompanied by severe arthralgia. Despite its high potential for urban emergence, MAYV is still an obscure virus with scarce information about its infection cycle, including the corresponding early events. Even for prototypical alphaviruses, the cell entry mechanism still has some rough edges to trim: although clathrin-mediated endocytosis is quoted as the putative route, alternative paths as distinct as direct virus genome injection through the cell plasma membrane seems to be possible. Our aim was to clarify crucial details on the entry route exploited by MAYV to gain access into the host cell. Tracking the virus since its first contact with the surface of Vero cells by fluorescence microscopy, we show that its entry occurs by a fast endocytic process and relies on fusion with acidic endosomal compartments. Moreover, blocking clathrin-mediated endocytosis or depleting cholesterol from the cell membrane leads to a strong inhibition of viral infection, as assessed by plaque assays. Following this clue, we found that early endosomes and caveolae-derived vesicles are both implicated as target membranes for MAYV fusion. Our findings unravel the very first events that culminate in a productive infection by MAYV and shed light on potential targets for a rational antiviral therapy, besides providing a better comprehension of the entry routes exploited by alphaviruses to get into the cell. |
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Carvalho, Carlos A. MSilva, Jerson LOliveira, Andrea Carvalho deGomes, Andre M. O2017-11-24T13:43:43Z2017-11-24T13:43:43Z2017CARVALHO, Carlos A. M. et al. On the entry of an emerging arbovirus into host cells: Mayaro virus takes the highway to the cytoplasm through fusion with early endosomes and caveolae-derived vesicles. PeerJ, v. 5, n. e3245, p. 1-18, Apr. 2017.2167-8359https://patua.iec.gov.br/handle/iec/287810.7717/peerj.3245Mayaro virus (MAYV) is an emergent sylvatic alphavirus in South America, related to sporadic outbreaks of a chikungunya-like human febrile illness accompanied by severe arthralgia. Despite its high potential for urban emergence, MAYV is still an obscure virus with scarce information about its infection cycle, including the corresponding early events. Even for prototypical alphaviruses, the cell entry mechanism still has some rough edges to trim: although clathrin-mediated endocytosis is quoted as the putative route, alternative paths as distinct as direct virus genome injection through the cell plasma membrane seems to be possible. Our aim was to clarify crucial details on the entry route exploited by MAYV to gain access into the host cell. Tracking the virus since its first contact with the surface of Vero cells by fluorescence microscopy, we show that its entry occurs by a fast endocytic process and relies on fusion with acidic endosomal compartments. Moreover, blocking clathrin-mediated endocytosis or depleting cholesterol from the cell membrane leads to a strong inhibition of viral infection, as assessed by plaque assays. Following this clue, we found that early endosomes and caveolae-derived vesicles are both implicated as target membranes for MAYV fusion. Our findings unravel the very first events that culminate in a productive infection by MAYV and shed light on potential targets for a rational antiviral therapy, besides providing a better comprehension of the entry routes exploited by alphaviruses to get into the cell.This work was supported by grants from Coordenacão de Aperfei ¸ coamento de Pessoal de ¸ Nível Superior (CAPES), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundacão de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), ¸ Financiadora de Estudos e Projetos (FINEP), Instituto Nacional de Ciência e Tecnologia de Biologia Estrutural e Bioimagem (INBEB) and Programa de Apoio a Núcleos de Excelência (PRONEX)Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil / Universidade Federal do Rio de Janeiro. Instituto de Bioquímica Médica Leopoldo de Meis. Programa de Biologia Estrutural. Rio de Janeiro, RJ, Brazil / Universidade Federal do Rio de Janeiro. Instituto Nacional de Ciência e Tecnologia de Biologia Estrutural e Bioimagem. Rio de Janeiro, RJ, Brazil.Universidade Federal do Rio de Janeiro. Instituto de Bioquímica Médica Leopoldo de Meis. Programa de Biologia Estrutural. Rio de Janeiro, RJ, Brazil / Universidade Federal do Rio de Janeiro. Instituto Nacional de Ciência e Tecnologia de Biologia Estrutural e Bioimagem. Rio de Janeiro, RJ, Brazil.Universidade Federal do Rio de Janeiro. Instituto de Bioquímica Médica Leopoldo de Meis. Programa de Biologia Estrutural. Rio de Janeiro, RJ, Brazil / Universidade Federal do Rio de Janeiro. Instituto Nacional de Ciência e Tecnologia de Biologia Estrutural e Bioimagem. Rio de Janeiro, RJ, Brazil.Universidade Federal do Rio de Janeiro. Instituto de Bioquímica Médica Leopoldo de Meis. Programa de Biologia Estrutural. Rio de Janeiro, RJ, Brazil / Universidade Federal do Rio de Janeiro. Instituto Nacional de Ciência e Tecnologia de Biologia Estrutural e Bioimagem. Rio de Janeiro, RJ, Brazil.engPeerJOn the entry of an emerging arbovirus into host cells: Mayaro virus takes the highway to the cytoplasm through fusion with early endosomes and caveolae-derived vesiclesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleAlphavirus / fisiologiaAlphavirus / crescimento & desenvolvimentoMembrana Celular / virologiaVesículas Revestidas por Clatrina / metabolismoCavéolas / metabolismoEndossomos / metabolismoInternalização do VírusCélulas CultivadasCélulas VeroFatores de TempoTemperatura AmbienteEnsaio de Placa Viral / métodosMicroscopia de Fluorescência / métodosinfo:eu-repo/semantics/openAccessreponame:Repositório Digital do Instituto Evandro Chagas (Patuá)instname:Instituto Evandro Chagas (IEC)instacron:IECORIGINALOn the entry of an emerging arbovirus into host cells: Mayaro virus takes the highway to the cytoplasm through fusion with early endosomes and caveolae-derived vesicles.pdfOn the entry of an emerging arbovirus into host cells: Mayaro virus takes the highway to the cytoplasm through fusion with early endosomes and caveolae-derived vesicles.pdfapplication/pdf13725143https://patua.iec.gov.br/bitstreams/31c2dd8a-7f42-4cb7-b5df-68a80547e16c/download3e6a45185403cf19fe8d3e0626ca4522MD51LICENSElicense.txtlicense.txttext/plain; charset=utf-871https://patua.iec.gov.br/bitstreams/d70a785b-0b12-4e12-90c0-be4a8af2d6b3/download52f1732ea66fbd1123abe39f5373b797MD52TEXTOn the entry of an emerging arbovirus into host cells: Mayaro virus takes the highway to the cytoplasm through fusion with early endosomes and caveolae-derived vesicles.pdf.txtOn the entry of an emerging arbovirus into host cells: Mayaro virus takes the highway to the cytoplasm through fusion with early endosomes and caveolae-derived vesicles.pdf.txtExtracted texttext/plain51329https://patua.iec.gov.br/bitstreams/22e78c3f-fb49-4739-828d-27cc26d79205/downloade02a486c1bade2b0bcb46f47a1b33baeMD55THUMBNAILOn the entry of an emerging arbovirus into host cells: Mayaro virus takes the highway to the cytoplasm through fusion with early endosomes and caveolae-derived vesicles.pdf.jpgOn the entry of an emerging arbovirus into host cells: Mayaro virus takes the highway to the cytoplasm through fusion with early endosomes and caveolae-derived vesicles.pdf.jpgGenerated Thumbnailimage/jpeg5906https://patua.iec.gov.br/bitstreams/dcf5f44a-8a43-4abf-9da1-ddbe5b22be97/download6a8e23f1237e40e3c4cb1256b3a4204dMD56iec/28782022-10-21 00:43:02.981oai:patua.iec.gov.br:iec/2878https://patua.iec.gov.brRepositório InstitucionalPUBhttps://patua.iec.gov.br/oai/requestclariceneta@iec.gov.br || Biblioteca@iec.gov.bropendoar:2022-10-21T00:43:02Repositório Digital do Instituto Evandro Chagas (Patuá) - Instituto Evandro Chagas (IEC)falseVG9kb3Mgb3MgZG9jdW1lbnRvcyBkZXNzYSBjb2xlw6fDo28gc2VndWVtIGEgTGljZW7Dp2EgQ3JlYXRpdmUgY29tbW9ucy4= |
dc.title.pt_BR.fl_str_mv |
On the entry of an emerging arbovirus into host cells: Mayaro virus takes the highway to the cytoplasm through fusion with early endosomes and caveolae-derived vesicles |
title |
On the entry of an emerging arbovirus into host cells: Mayaro virus takes the highway to the cytoplasm through fusion with early endosomes and caveolae-derived vesicles |
spellingShingle |
On the entry of an emerging arbovirus into host cells: Mayaro virus takes the highway to the cytoplasm through fusion with early endosomes and caveolae-derived vesicles Carvalho, Carlos A. M Alphavirus / fisiologia Alphavirus / crescimento & desenvolvimento Membrana Celular / virologia Vesículas Revestidas por Clatrina / metabolismo Cavéolas / metabolismo Endossomos / metabolismo Internalização do Vírus Células Cultivadas Células Vero Fatores de Tempo Temperatura Ambiente Ensaio de Placa Viral / métodos Microscopia de Fluorescência / métodos |
title_short |
On the entry of an emerging arbovirus into host cells: Mayaro virus takes the highway to the cytoplasm through fusion with early endosomes and caveolae-derived vesicles |
title_full |
On the entry of an emerging arbovirus into host cells: Mayaro virus takes the highway to the cytoplasm through fusion with early endosomes and caveolae-derived vesicles |
title_fullStr |
On the entry of an emerging arbovirus into host cells: Mayaro virus takes the highway to the cytoplasm through fusion with early endosomes and caveolae-derived vesicles |
title_full_unstemmed |
On the entry of an emerging arbovirus into host cells: Mayaro virus takes the highway to the cytoplasm through fusion with early endosomes and caveolae-derived vesicles |
title_sort |
On the entry of an emerging arbovirus into host cells: Mayaro virus takes the highway to the cytoplasm through fusion with early endosomes and caveolae-derived vesicles |
author |
Carvalho, Carlos A. M |
author_facet |
Carvalho, Carlos A. M Silva, Jerson L Oliveira, Andrea Carvalho de Gomes, Andre M. O |
author_role |
author |
author2 |
Silva, Jerson L Oliveira, Andrea Carvalho de Gomes, Andre M. O |
author2_role |
author author author |
dc.contributor.author.fl_str_mv |
Carvalho, Carlos A. M Silva, Jerson L Oliveira, Andrea Carvalho de Gomes, Andre M. O |
dc.subject.decsPrimary.pt_BR.fl_str_mv |
Alphavirus / fisiologia Alphavirus / crescimento & desenvolvimento Membrana Celular / virologia Vesículas Revestidas por Clatrina / metabolismo Cavéolas / metabolismo Endossomos / metabolismo Internalização do Vírus Células Cultivadas Células Vero Fatores de Tempo Temperatura Ambiente Ensaio de Placa Viral / métodos Microscopia de Fluorescência / métodos |
topic |
Alphavirus / fisiologia Alphavirus / crescimento & desenvolvimento Membrana Celular / virologia Vesículas Revestidas por Clatrina / metabolismo Cavéolas / metabolismo Endossomos / metabolismo Internalização do Vírus Células Cultivadas Células Vero Fatores de Tempo Temperatura Ambiente Ensaio de Placa Viral / métodos Microscopia de Fluorescência / métodos |
description |
Mayaro virus (MAYV) is an emergent sylvatic alphavirus in South America, related to sporadic outbreaks of a chikungunya-like human febrile illness accompanied by severe arthralgia. Despite its high potential for urban emergence, MAYV is still an obscure virus with scarce information about its infection cycle, including the corresponding early events. Even for prototypical alphaviruses, the cell entry mechanism still has some rough edges to trim: although clathrin-mediated endocytosis is quoted as the putative route, alternative paths as distinct as direct virus genome injection through the cell plasma membrane seems to be possible. Our aim was to clarify crucial details on the entry route exploited by MAYV to gain access into the host cell. Tracking the virus since its first contact with the surface of Vero cells by fluorescence microscopy, we show that its entry occurs by a fast endocytic process and relies on fusion with acidic endosomal compartments. Moreover, blocking clathrin-mediated endocytosis or depleting cholesterol from the cell membrane leads to a strong inhibition of viral infection, as assessed by plaque assays. Following this clue, we found that early endosomes and caveolae-derived vesicles are both implicated as target membranes for MAYV fusion. Our findings unravel the very first events that culminate in a productive infection by MAYV and shed light on potential targets for a rational antiviral therapy, besides providing a better comprehension of the entry routes exploited by alphaviruses to get into the cell. |
publishDate |
2017 |
dc.date.accessioned.fl_str_mv |
2017-11-24T13:43:43Z |
dc.date.available.fl_str_mv |
2017-11-24T13:43:43Z |
dc.date.issued.fl_str_mv |
2017 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
CARVALHO, Carlos A. M. et al. On the entry of an emerging arbovirus into host cells: Mayaro virus takes the highway to the cytoplasm through fusion with early endosomes and caveolae-derived vesicles. PeerJ, v. 5, n. e3245, p. 1-18, Apr. 2017. |
dc.identifier.uri.fl_str_mv |
https://patua.iec.gov.br/handle/iec/2878 |
dc.identifier.issn.-.fl_str_mv |
2167-8359 |
dc.identifier.doi.-.fl_str_mv |
10.7717/peerj.3245 |
identifier_str_mv |
CARVALHO, Carlos A. M. et al. On the entry of an emerging arbovirus into host cells: Mayaro virus takes the highway to the cytoplasm through fusion with early endosomes and caveolae-derived vesicles. PeerJ, v. 5, n. e3245, p. 1-18, Apr. 2017. 2167-8359 10.7717/peerj.3245 |
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https://patua.iec.gov.br/handle/iec/2878 |
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eng |
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eng |
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PeerJ |
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PeerJ |
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