Avaliação do perfil de miRNA alterados no plasma de pacientes infectados com o vírus ZIKA

Detalhes bibliográficos
Ano de defesa: 2022
Autor(a) principal: ANA CAROLINA CARVALHO SILVA
Orientador(a): Não Informado pela instituição
Banca de defesa: Não Informado pela instituição
Tipo de documento: Tese
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Universidade Federal de Minas Gerais
Programa de Pós-Graduação: Não Informado pela instituição
Departamento: Não Informado pela instituição
País: Não Informado pela instituição
Palavras-chave em Português:
Link de acesso: https://hdl.handle.net/1843/82146
Resumo: The Zika virus (ZIKV) is an arbovirus member of the family Flaviviridae and genus Flavivirus generally transmitted by mosquitoes of the genus Aedes. The clinical presentation of ZIKV is not specific (fever, skin rash, arthralgia, myalgia, anorexia and asthenia) and can be confused with other diseases, especially dengue and Chikungunya. In 2015, the first cases of ZIKV infection in Brazil were reported, as well as the association of the infection with the development of microcephaly and Guillain-Barré syndrome. The immunological and molecular mechanisms related to the response to infection with ZIKV have yet to be elucidated. The identification of molecular mechanisms responsible for the modulation, in the host, of several pathways in response to ZIKV is the first step towards finding potential therapeutic targets for the control of infection and treatment of symptoms. In the last decade it has been demonstrated that microRNAs (miRNAs), small RNA molecules of 22 nucleotides, are involved in the regulation of gene expression in virtually all cellular processes. miRNAs have also been identified as important plasma biomarkers, as they are secreted by cells or released during tissue damage and infections. It is known that different viral infections induce a change in the expression profile, as well as in the content of miRNAs circulating in the plasma of infected patients. However, there are still no studies that have studied the importance and alteration of circulating miRNAs during infection with ZIKV. In this work, we evaluated the circulating miRNAs profiles of plasma samples that were collected from patients in the acute and convalescent phases of ZIKV infection and from healthy individuals in the same endemic region. The miRNA profile of the groups was obtained and analyzed. We observed that infection with ZIKV caused changes in the profile of circulating miRNAs, as expected. This profile was different from convalescent patients and healthy patients. Using bioinformatics and systems biology tools, we predict potential targets of altered miRNAs as well as the signaling pathways they potentially control. Among the twenty-four differentially expressed miRNAs (DEMs), we highlight miR-146, miR-125a-5p, miR-30-5p and miR-142-3p identified and related to signaling pathways modulated during infection. The results presented here are an effort to open new avenues for the key roles of miRNAs during ZIKV infection.
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spelling 2025-05-08T17:10:07Z2025-09-09T01:32:22Z2025-05-08T17:10:07Z2022-03-30https://hdl.handle.net/1843/82146The Zika virus (ZIKV) is an arbovirus member of the family Flaviviridae and genus Flavivirus generally transmitted by mosquitoes of the genus Aedes. The clinical presentation of ZIKV is not specific (fever, skin rash, arthralgia, myalgia, anorexia and asthenia) and can be confused with other diseases, especially dengue and Chikungunya. In 2015, the first cases of ZIKV infection in Brazil were reported, as well as the association of the infection with the development of microcephaly and Guillain-Barré syndrome. The immunological and molecular mechanisms related to the response to infection with ZIKV have yet to be elucidated. The identification of molecular mechanisms responsible for the modulation, in the host, of several pathways in response to ZIKV is the first step towards finding potential therapeutic targets for the control of infection and treatment of symptoms. In the last decade it has been demonstrated that microRNAs (miRNAs), small RNA molecules of 22 nucleotides, are involved in the regulation of gene expression in virtually all cellular processes. miRNAs have also been identified as important plasma biomarkers, as they are secreted by cells or released during tissue damage and infections. It is known that different viral infections induce a change in the expression profile, as well as in the content of miRNAs circulating in the plasma of infected patients. However, there are still no studies that have studied the importance and alteration of circulating miRNAs during infection with ZIKV. In this work, we evaluated the circulating miRNAs profiles of plasma samples that were collected from patients in the acute and convalescent phases of ZIKV infection and from healthy individuals in the same endemic region. The miRNA profile of the groups was obtained and analyzed. We observed that infection with ZIKV caused changes in the profile of circulating miRNAs, as expected. This profile was different from convalescent patients and healthy patients. Using bioinformatics and systems biology tools, we predict potential targets of altered miRNAs as well as the signaling pathways they potentially control. Among the twenty-four differentially expressed miRNAs (DEMs), we highlight miR-146, miR-125a-5p, miR-30-5p and miR-142-3p identified and related to signaling pathways modulated during infection. The results presented here are an effort to open new avenues for the key roles of miRNAs during ZIKV infection.CNPq - Conselho Nacional de Desenvolvimento Científico e TecnológicoporUniversidade Federal de Minas Geraishttp://creativecommons.org/licenses/by-nc-nd/3.0/pt/info:eu-repo/semantics/openAccessVírus ZIKAmiRNABiologia CelularInfecção por Zika virusMicroRNAsAvaliação do perfil de miRNA alterados no plasma de pacientes infectados com o vírus ZIKAinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisANA CAROLINA CARVALHO SILVAreponame:Repositório Institucional da UFMGinstname:Universidade Federal de Minas Gerais (UFMG)instacron:UFMGhttp://lattes.cnpq.br/1477398001855695Ludmila Rodrigues Pinto Ferreira Camargohttp://lattes.cnpq.br/8557103889978152O vírus Zika (ZIKV) é um arbovírus membro da família Flaviviridae e gênero Flavivirus geralmente transmitido por mosquitos do gênero Aedes. A apresentação clínica do ZIKV não é específica (febre, rash cutâneo, artralgia, mialgia, anorexia e astenia) podendo ser confundida com outras doenças, especialmente dengue e chikungunya. Em 2015 relatou-se os primeiros casos de infecção com ZIKV no Brasil assim como a associação da infecção com o desenvolvimento de microcefalia e da síndrome Guillain-Barré. Os mecanismos imunológicos e moleculares relacionados à resposta a infecção com ZIKV ainda precisam ser elucidadas. A identificação de mecanismos moleculares responsáveis pela modulação, no hospedeiro, de diversas vias em resposta ao ZIKV é o primeiro passo para que se encontrem alvos terapêuticos em potencial para o controle da infecção e tratamento dos sintomas. Na última década foi demonstrado que microRNAs (miRNAs), pequenas moléculas de RNA de 22 nucleotídeos, estão envolvidas na regulação da expressão gênica de virtualmente todos os processos celulares. Os miRNAs também têm sido identificados como importantes biomarcadores plasmáticos, pois são secretados pelas células ou liberados durante dano tecidual e infecções. Sabe-se que diferentes infecções virais induzem uma alteração no perfil de expressão de miRNAs circulantes no plasma de pacientes infectados. Entretanto, ainda não existem trabalhos que estudaram a importância e alteração desses miRNAs durante a infecção com ZIKV. Neste trabalho nós avaliamos o perfil de miRNAs circulantes em amostras de plasma que foram coletadas de pacientes nas fases aguda e de convalescência da infecção por ZIKV e de pacientes saudáveis provenientes da mesma região endêmica. O perfil de miRNAs dos grupos foi obtido e analisado. Observamos que a infecção com ZIKV causou alterações no perfil de miRNAs circulantes, como esperado. Esse perfil foi distinto dos pacientes convalescentes e dos pacientes saudáveis. Por meio da utilização de ferramentas de bioinformática e biologia de sistemas predizemos alvos em potencial dos miRNAs alterados assim como vias de sinalização que estes potencialmente controlam. Dentre os vinte e quatro miRNAs diferencialmente expressos (DEMs), destacamos os miR-146, miR-125a-5p, miR-30-5p e miR-142-3p identificados e relacionados a vias de sinalização moduladas durante a infecção. Os resultados aqui apresentados são um esforço para abrir novos caminhos para os principais papéis dos miRNAs durante a infecção pelo ZIKV.BrasilPrograma de Pós-Graduação em Biologia CelularUFMGORIGINALTESE_ANA_REPOSITÓRIO.pdfapplication/pdf2286012https://repositorio.ufmg.br//bitstreams/cd62f6d9-1de4-4a3a-b4b8-d09e24557f46/downloadee7e9c069787112d80d2c172be52c7b4MD51trueAnonymousREADCC-LICENSElicense_rdfapplication/octet-stream811https://repositorio.ufmg.br//bitstreams/e5551eb8-ac58-4d53-ad1b-75184e16cce1/downloadcfd6801dba008cb6adbd9838b81582abMD52falseAnonymousREADLICENSElicense.txttext/plain2118https://repositorio.ufmg.br//bitstreams/74c9613f-6b5b-40e6-9546-e2f0ce2e41e2/downloadcda590c95a0b51b4d15f60c9642ca272MD53falseAnonymousREAD1843/821462025-09-08 22:32:22.797http://creativecommons.org/licenses/by-nc-nd/3.0/pt/Acesso Abertoopen.accessoai:repositorio.ufmg.br:1843/82146https://repositorio.ufmg.br/Repositório InstitucionalPUBhttps://repositorio.ufmg.br/oairepositorio@ufmg.bropendoar:2025-09-09T01:32:22Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)falseTElDRU7Dh0EgREUgRElTVFJJQlVJw4fDg08gTsODTy1FWENMVVNJVkEgRE8gUkVQT1NJVMOTUklPIElOU1RJVFVDSU9OQUwgREEgVUZNRwoKQ29tIGEgYXByZXNlbnRhw6fDo28gZGVzdGEgbGljZW7Dp2EsIHZvY8OqIChvIGF1dG9yIChlcykgb3UgbyB0aXR1bGFyIGRvcyBkaXJlaXRvcyBkZSBhdXRvcikgY29uY2VkZSBhbyBSZXBvc2l0w7NyaW8gSW5zdGl0dWNpb25hbCBkYSBVRk1HIChSSS1VRk1HKSBvIGRpcmVpdG8gbsOjbyBleGNsdXNpdm8gZSBpcnJldm9nw6F2ZWwgZGUgcmVwcm9kdXppciBlL291IGRpc3RyaWJ1aXIgYSBzdWEgcHVibGljYcOnw6NvIChpbmNsdWluZG8gbyByZXN1bW8pIHBvciB0b2RvIG8gbXVuZG8gbm8gZm9ybWF0byBpbXByZXNzbyBlIGVsZXRyw7RuaWNvIGUgZW0gcXVhbHF1ZXIgbWVpbywgaW5jbHVpbmRvIG9zIGZvcm1hdG9zIMOhdWRpbyBvdSB2w61kZW8uCgpWb2PDqiBkZWNsYXJhIHF1ZSBjb25oZWNlIGEgcG9sw610aWNhIGRlIGNvcHlyaWdodCBkYSBlZGl0b3JhIGRvIHNldSBkb2N1bWVudG8gZSBxdWUgY29uaGVjZSBlIGFjZWl0YSBhcyBEaXJldHJpemVzIGRvIFJJLVVGTUcuCgpWb2PDqiBjb25jb3JkYSBxdWUgbyBSZXBvc2l0w7NyaW8gSW5zdGl0dWNpb25hbCBkYSBVRk1HIHBvZGUsIHNlbSBhbHRlcmFyIG8gY29udGXDumRvLCB0cmFuc3BvciBhIHN1YSBwdWJsaWNhw6fDo28gcGFyYSBxdWFscXVlciBtZWlvIG91IGZvcm1hdG8gcGFyYSBmaW5zIGRlIHByZXNlcnZhw6fDo28uCgpWb2PDqiB0YW1iw6ltIGNvbmNvcmRhIHF1ZSBvIFJlcG9zaXTDs3JpbyBJbnN0aXR1Y2lvbmFsIGRhIFVGTUcgcG9kZSBtYW50ZXIgbWFpcyBkZSB1bWEgY8OzcGlhIGRlIHN1YSBwdWJsaWNhw6fDo28gcGFyYSBmaW5zIGRlIHNlZ3VyYW7Dp2EsIGJhY2stdXAgZSBwcmVzZXJ2YcOnw6NvLgoKVm9jw6ogZGVjbGFyYSBxdWUgYSBzdWEgcHVibGljYcOnw6NvIMOpIG9yaWdpbmFsIGUgcXVlIHZvY8OqIHRlbSBvIHBvZGVyIGRlIGNvbmNlZGVyIG9zIGRpcmVpdG9zIGNvbnRpZG9zIG5lc3RhIGxpY2Vuw6dhLiBWb2PDqiB0YW1iw6ltIGRlY2xhcmEgcXVlIG8gZGVww7NzaXRvIGRlIHN1YSBwdWJsaWNhw6fDo28gbsOjbywgcXVlIHNlamEgZGUgc2V1IGNvbmhlY2ltZW50bywgaW5mcmluZ2UgZGlyZWl0b3MgYXV0b3JhaXMgZGUgbmluZ3XDqW0uCgpDYXNvIGEgc3VhIHB1YmxpY2HDp8OjbyBjb250ZW5oYSBtYXRlcmlhbCBxdWUgdm9jw6ogbsOjbyBwb3NzdWkgYSB0aXR1bGFyaWRhZGUgZG9zIGRpcmVpdG9zIGF1dG9yYWlzLCB2b2PDqiBkZWNsYXJhIHF1ZSBvYnRldmUgYSBwZXJtaXNzw6NvIGlycmVzdHJpdGEgZG8gZGV0ZW50b3IgZG9zIGRpcmVpdG9zIGF1dG9yYWlzIHBhcmEgY29uY2VkZXIgYW8gUmVwb3NpdMOzcmlvIEluc3RpdHVjaW9uYWwgZGEgVUZNRyBvcyBkaXJlaXRvcyBhcHJlc2VudGFkb3MgbmVzdGEgbGljZW7Dp2EsIGUgcXVlIGVzc2UgbWF0ZXJpYWwgZGUgcHJvcHJpZWRhZGUgZGUgdGVyY2Vpcm9zIGVzdMOhIGNsYXJhbWVudGUgaWRlbnRpZmljYWRvIGUgcmVjb25oZWNpZG8gbm8gdGV4dG8gb3Ugbm8gY29udGXDumRvIGRhIHB1YmxpY2HDp8OjbyBvcmEgZGVwb3NpdGFkYS4KCkNBU08gQSBQVUJMSUNBw4fDg08gT1JBIERFUE9TSVRBREEgVEVOSEEgU0lETyBSRVNVTFRBRE8gREUgVU0gUEFUUk9Dw41OSU8gT1UgQVBPSU8gREUgVU1BIEFHw4pOQ0lBIERFIEZPTUVOVE8gT1UgT1VUUk8gT1JHQU5JU01PLCBWT0PDiiBERUNMQVJBIFFVRSBSRVNQRUlUT1UgVE9ET1MgRSBRVUFJU1FVRVIgRElSRUlUT1MgREUgUkVWSVPDg08gQ09NTyBUQU1Cw4lNIEFTIERFTUFJUyBPQlJJR0HDh8OVRVMgRVhJR0lEQVMgUE9SIENPTlRSQVRPIE9VIEFDT1JETy4KCk8gUmVwb3NpdMOzcmlvIEluc3RpdHVjaW9uYWwgZGEgVUZNRyBzZSBjb21wcm9tZXRlIGEgaWRlbnRpZmljYXIgY2xhcmFtZW50ZSBvIHNldSBub21lKHMpIG91IG8ocykgbm9tZXMocykgZG8ocykgZGV0ZW50b3IoZXMpIGRvcyBkaXJlaXRvcyBhdXRvcmFpcyBkYSBwdWJsaWNhw6fDo28sIGUgbsOjbyBmYXLDoSBxdWFscXVlciBhbHRlcmHDp8OjbywgYWzDqW0gZGFxdWVsYXMgY29uY2VkaWRhcyBwb3IgZXN0YSBsaWNlbsOnYS4K
dc.title.none.fl_str_mv Avaliação do perfil de miRNA alterados no plasma de pacientes infectados com o vírus ZIKA
title Avaliação do perfil de miRNA alterados no plasma de pacientes infectados com o vírus ZIKA
spellingShingle Avaliação do perfil de miRNA alterados no plasma de pacientes infectados com o vírus ZIKA
ANA CAROLINA CARVALHO SILVA
Biologia Celular
Infecção por Zika virus
MicroRNAs
Vírus ZIKA
miRNA
title_short Avaliação do perfil de miRNA alterados no plasma de pacientes infectados com o vírus ZIKA
title_full Avaliação do perfil de miRNA alterados no plasma de pacientes infectados com o vírus ZIKA
title_fullStr Avaliação do perfil de miRNA alterados no plasma de pacientes infectados com o vírus ZIKA
title_full_unstemmed Avaliação do perfil de miRNA alterados no plasma de pacientes infectados com o vírus ZIKA
title_sort Avaliação do perfil de miRNA alterados no plasma de pacientes infectados com o vírus ZIKA
author ANA CAROLINA CARVALHO SILVA
author_facet ANA CAROLINA CARVALHO SILVA
author_role author
dc.contributor.author.fl_str_mv ANA CAROLINA CARVALHO SILVA
dc.subject.por.fl_str_mv Biologia Celular
Infecção por Zika virus
MicroRNAs
topic Biologia Celular
Infecção por Zika virus
MicroRNAs
Vírus ZIKA
miRNA
dc.subject.other.none.fl_str_mv Vírus ZIKA
miRNA
description The Zika virus (ZIKV) is an arbovirus member of the family Flaviviridae and genus Flavivirus generally transmitted by mosquitoes of the genus Aedes. The clinical presentation of ZIKV is not specific (fever, skin rash, arthralgia, myalgia, anorexia and asthenia) and can be confused with other diseases, especially dengue and Chikungunya. In 2015, the first cases of ZIKV infection in Brazil were reported, as well as the association of the infection with the development of microcephaly and Guillain-Barré syndrome. The immunological and molecular mechanisms related to the response to infection with ZIKV have yet to be elucidated. The identification of molecular mechanisms responsible for the modulation, in the host, of several pathways in response to ZIKV is the first step towards finding potential therapeutic targets for the control of infection and treatment of symptoms. In the last decade it has been demonstrated that microRNAs (miRNAs), small RNA molecules of 22 nucleotides, are involved in the regulation of gene expression in virtually all cellular processes. miRNAs have also been identified as important plasma biomarkers, as they are secreted by cells or released during tissue damage and infections. It is known that different viral infections induce a change in the expression profile, as well as in the content of miRNAs circulating in the plasma of infected patients. However, there are still no studies that have studied the importance and alteration of circulating miRNAs during infection with ZIKV. In this work, we evaluated the circulating miRNAs profiles of plasma samples that were collected from patients in the acute and convalescent phases of ZIKV infection and from healthy individuals in the same endemic region. The miRNA profile of the groups was obtained and analyzed. We observed that infection with ZIKV caused changes in the profile of circulating miRNAs, as expected. This profile was different from convalescent patients and healthy patients. Using bioinformatics and systems biology tools, we predict potential targets of altered miRNAs as well as the signaling pathways they potentially control. Among the twenty-four differentially expressed miRNAs (DEMs), we highlight miR-146, miR-125a-5p, miR-30-5p and miR-142-3p identified and related to signaling pathways modulated during infection. The results presented here are an effort to open new avenues for the key roles of miRNAs during ZIKV infection.
publishDate 2022
dc.date.issued.fl_str_mv 2022-03-30
dc.date.accessioned.fl_str_mv 2025-05-08T17:10:07Z
2025-09-09T01:32:22Z
dc.date.available.fl_str_mv 2025-05-08T17:10:07Z
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publisher.none.fl_str_mv Universidade Federal de Minas Gerais
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