Mapeamento imunoinformático de regiões conservadas da proteína hexon de adenovírus humano
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Repositório Institucional da UFG |
Texto Completo: | http://repositorio.bc.ufg.br/tede/handle/tede/10560 |
Resumo: | Human Adenoviruses (HAdVs) are important infectious agents associated with high incidence, morbidity and mortality in immunocompromised patients, such as those undergoing allogeneic hematopoietic progenitor cell transplantation (allo-TCPH). HAdVs belong to the family Adenoviridae, genus Mastadenovirus, and further classified into seven species (A-G) and 103 genotypes, characterized so far. The HAdV capsid consists mainly of the hexon protein, which has four highly conserved regions (CR1 - 4) that are known for their immunogenic potential, being one of the main targets of the T and B cell-mediated anti-HAdV immune response. The aim of the present study was to perform the mapping of potentially immunogenic epitopes, located in the HAdV hexon CRs and to evaluate the HAdV infection in patients undergoing allo-TCPH. To this end, predictions of T and B cell epitopes and IFN-γ induction were performed, considering 101 HAdV genotypes with sequences available in databases. The most conserved and best classified epitopes were then selected by the prediction programs to perform the molecular docking analysis with HLA alleles of the study population, consisting of nine adult patients undergoing allo-TCPH. It was also carried out the HAdV research by TaqMan real-time polymerase chain reaction (qPCR) in the patient's serum samples. As a result, regions containing overlapping T and B cell epitopes were obtained and, based on immunoinformatics analysis (prediction and molecular docking), two peptides with high conservation and immunogenic potential were designed. Nine patients were positive for HAdV by qPCR TaqMan, with the average viral load found in the serum samples of the study population being 6.71x1011 CG / mL. The genomic sequencing of the positive samples returned sequences that showed 100% similarity with sequences of the HAdV C hexon protein, deposited in a database. The present study allowed the mapping of the main immunogenic regions located in the CRs of the HAdV hexon, as well as the construction of two peptides that will be used in future studies to evaluate the immune response of patients undergoing allo-TCPH, participating in the present study. |
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Souza, Menira Borges de Lima Dias ehttp://lattes.cnpq.br/0054562567103606Souza, Menira Borges de Lima Dias eFonseca, Simone Gonçalves daGardinassi, Luiz Gustavo Araújohttp://lattes.cnpq.br/5347902022546012Anjos, Déborah Carolina Carvalho dos2020-09-04T12:14:48Z2020-09-04T12:14:48Z2020-03-17ANJOS, D. C. C. Mapeamento imunoinformático de regiões conservadas da proteína hexon de adenovírus humano. 2020. 89 f. Dissertação (Mestrado em Biologia da Relação Parasito-Hospedeiro) - Universidade Federal de Goiás, Goiânia, 2020.http://repositorio.bc.ufg.br/tede/handle/tede/10560ark:/38995/0013000005xp1Human Adenoviruses (HAdVs) are important infectious agents associated with high incidence, morbidity and mortality in immunocompromised patients, such as those undergoing allogeneic hematopoietic progenitor cell transplantation (allo-TCPH). HAdVs belong to the family Adenoviridae, genus Mastadenovirus, and further classified into seven species (A-G) and 103 genotypes, characterized so far. The HAdV capsid consists mainly of the hexon protein, which has four highly conserved regions (CR1 - 4) that are known for their immunogenic potential, being one of the main targets of the T and B cell-mediated anti-HAdV immune response. The aim of the present study was to perform the mapping of potentially immunogenic epitopes, located in the HAdV hexon CRs and to evaluate the HAdV infection in patients undergoing allo-TCPH. To this end, predictions of T and B cell epitopes and IFN-γ induction were performed, considering 101 HAdV genotypes with sequences available in databases. The most conserved and best classified epitopes were then selected by the prediction programs to perform the molecular docking analysis with HLA alleles of the study population, consisting of nine adult patients undergoing allo-TCPH. It was also carried out the HAdV research by TaqMan real-time polymerase chain reaction (qPCR) in the patient's serum samples. As a result, regions containing overlapping T and B cell epitopes were obtained and, based on immunoinformatics analysis (prediction and molecular docking), two peptides with high conservation and immunogenic potential were designed. Nine patients were positive for HAdV by qPCR TaqMan, with the average viral load found in the serum samples of the study population being 6.71x1011 CG / mL. The genomic sequencing of the positive samples returned sequences that showed 100% similarity with sequences of the HAdV C hexon protein, deposited in a database. The present study allowed the mapping of the main immunogenic regions located in the CRs of the HAdV hexon, as well as the construction of two peptides that will be used in future studies to evaluate the immune response of patients undergoing allo-TCPH, participating in the present study.Os Adenovírus Humanos (HAdVs) são importantes agentes infecciosos associados a elevada incidência e morbimortalidade em pacientes imunocomprometidos, como os submetidos a transplante alogênico de células progenitoras hematopoiéticas (alo-TCPH). Os HAdVs pertencem à família Adenoviridae, gênero Mastadenovirus, sendo ainda classificados em sete espécies (A-G) e 103 genótipos, caracterizados até o momento. O capsídeo de HAdV é constituído, majoritariamente pela proteína hexon, que apresenta quatro regiões altamente conservadas (CR1 – 4) e conhecidas por seu potencial imunogênico, sendo um dos principais alvos da resposta imune anti- HAdV mediada por células T e B. O objetivo do presente estudo foi realizar o mapeamento de epítopos potencialmente imunogênicos, localizados nas CRs da hexon de HAdV e avaliar a infecção por HAdV em pacientes submetidos ao alo-TCPH. Para tal, foram realizadas as predições de epítopos de células T e B e indução de IFN-γ, considerando 101 genótipos de HAdV com sequências disponíveis em bancos de dados. Foram então selecionados os epítopos mais conservados e melhores classificados pelos programas de predição para realizar a análise de docking molecular com alelos de HLA da população de estudo, constituída por nove pacientes adultos submetidos ao alo-TCPH. Foi realizada ainda, a pesquisa de HAdV por reação em cadeia da polimerase em tempo real (qPCR) TaqMan nas amostras de soro dos pacientes. Foram obtidas, como resultado, regiões contendo sobreposição de epítopos de células T e B e, com base nas análises imunoinformáticas (predição e docking molecular), foram desenhados dois peptídeos com elevada conservação e potencial imunogênico. Nove pacientes foram positivos para HAdV por qPCR TaqMan, sendo a carga viral média encontrada nas amostras de soro da população de estudo de 6,71x1011 CG/mL. O sequenciamento genômico das amostras positivas retornou sequências que apresentaram 100% de similaridade com sequências da proteína hexon de HAdV C, depositadas em banco de dados. O presente estudo permitiu o mapeamento das principais regiões imunogênicas localizadas nas CRs da hexon de HAdV, bem como a construção de dois peptídeos que serão utilizados em estudos futuros para a avaliação da resposta imune dos pacientes submetidos ao alo-TCPH, participantes do presente estudo.Submitted by Liliane Ferreira (ljuvencia30@gmail.com) on 2020-09-03T12:44:58Z No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) Dissertação - Déborah Carolina Carvalho dos Anjos - 2020.pdf: 2970442 bytes, checksum: 3158c90849fe84108feb030a17dd8b5d (MD5)Rejected by Luciana Ferreira (lucgeral@gmail.com), reason: No lattes pede para ser citada: Nome em citações bibliográficas - ANJOS, D. C. C on 2020-09-03T19:20:04Z (GMT)Submitted by Liliane Ferreira (ljuvencia30@gmail.com) on 2020-09-04T11:25:39Z No. of bitstreams: 2 Dissertação - Déborah Carolina Carvalho dos Anjos - 2020.pdf: 2970442 bytes, checksum: 3158c90849fe84108feb030a17dd8b5d (MD5) license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5)Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2020-09-04T12:14:48Z (GMT) No. of bitstreams: 2 Dissertação - Déborah Carolina Carvalho dos Anjos - 2020.pdf: 2970442 bytes, checksum: 3158c90849fe84108feb030a17dd8b5d (MD5) license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5)Made available in DSpace on 2020-09-04T12:14:48Z (GMT). No. of bitstreams: 2 Dissertação - Déborah Carolina Carvalho dos Anjos - 2020.pdf: 2970442 bytes, checksum: 3158c90849fe84108feb030a17dd8b5d (MD5) license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) Previous issue date: 2020-03-17Fundação de Amparo à Pesquisa do Estado de GoiásporUniversidade Federal de GoiásPrograma de Pós-graduação em Biologia da Relação Parasito-Hospedeiro (IPTSP)UFGBrasilInstituto de Patologia Tropical e Saúde Pública - IPTSP (RG)Attribution-NonCommercial-NoDerivs 3.0 Brazilhttp://creativecommons.org/licenses/by-nc-nd/3.0/br/info:eu-repo/semantics/openAccessAdenovírus humanoAlo-TCPHImunoinformáticaProteína hexonViremiaHuman adenovirusAllo-TCPHImmunoinformaticsHexon proteinviremiaCIENCIAS BIOLOGICAS::MICROBIOLOGIA::MICROBIOLOGIA APLICADAMapeamento imunoinformático de regiões conservadas da proteína hexon de adenovírus humanoImmunoinformatic mapping of conserved regions of hexon human adenovirus proteininfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesis15500500500500298743reponame:Repositório Institucional da UFGinstname:Universidade Federal de Goiás (UFG)instacron:UFGORIGINALDissertação - Déborah Carolina Carvalho dos Anjos - 2020.pdfDissertação - Déborah Carolina Carvalho dos Anjos - 2020.pdfapplication/pdf2970442http://repositorio.bc.ufg.br/tede/bitstreams/d5848021-2bab-4f59-98ca-8aa811e10bdd/download3158c90849fe84108feb030a17dd8b5dMD53LICENSElicense.txtlicense.txttext/plain; charset=utf-81748http://repositorio.bc.ufg.br/tede/bitstreams/f38eb943-f781-4fdc-a205-fd4bbbad5eb0/download8a4605be74aa9ea9d79846c1fba20a33MD54CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-8811http://repositorio.bc.ufg.br/tede/bitstreams/141b1cb1-0ba2-4612-aeaa-cb278fe41ddf/downloade39d27027a6cc9cb039ad269a5db8e34MD55tede/105602020-09-04 09:14:49.227http://creativecommons.org/licenses/by-nc-nd/3.0/br/Attribution-NonCommercial-NoDerivs 3.0 Brazilopen.accessoai:repositorio.bc.ufg.br:tede/10560http://repositorio.bc.ufg.br/tedeRepositório InstitucionalPUBhttp://repositorio.bc.ufg.br/oai/requesttasesdissertacoes.bc@ufg.bropendoar:2020-09-04T12:14:49Repositório Institucional da UFG - Universidade Federal de Goiás (UFG)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 |
dc.title.pt_BR.fl_str_mv |
Mapeamento imunoinformático de regiões conservadas da proteína hexon de adenovírus humano |
dc.title.alternative.eng.fl_str_mv |
Immunoinformatic mapping of conserved regions of hexon human adenovirus protein |
title |
Mapeamento imunoinformático de regiões conservadas da proteína hexon de adenovírus humano |
spellingShingle |
Mapeamento imunoinformático de regiões conservadas da proteína hexon de adenovírus humano Anjos, Déborah Carolina Carvalho dos Adenovírus humano Alo-TCPH Imunoinformática Proteína hexon Viremia Human adenovirus Allo-TCPH Immunoinformatics Hexon protein viremia CIENCIAS BIOLOGICAS::MICROBIOLOGIA::MICROBIOLOGIA APLICADA |
title_short |
Mapeamento imunoinformático de regiões conservadas da proteína hexon de adenovírus humano |
title_full |
Mapeamento imunoinformático de regiões conservadas da proteína hexon de adenovírus humano |
title_fullStr |
Mapeamento imunoinformático de regiões conservadas da proteína hexon de adenovírus humano |
title_full_unstemmed |
Mapeamento imunoinformático de regiões conservadas da proteína hexon de adenovírus humano |
title_sort |
Mapeamento imunoinformático de regiões conservadas da proteína hexon de adenovírus humano |
author |
Anjos, Déborah Carolina Carvalho dos |
author_facet |
Anjos, Déborah Carolina Carvalho dos |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Souza, Menira Borges de Lima Dias e |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/0054562567103606 |
dc.contributor.referee1.fl_str_mv |
Souza, Menira Borges de Lima Dias e |
dc.contributor.referee2.fl_str_mv |
Fonseca, Simone Gonçalves da |
dc.contributor.referee3.fl_str_mv |
Gardinassi, Luiz Gustavo Araújo |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/5347902022546012 |
dc.contributor.author.fl_str_mv |
Anjos, Déborah Carolina Carvalho dos |
contributor_str_mv |
Souza, Menira Borges de Lima Dias e Souza, Menira Borges de Lima Dias e Fonseca, Simone Gonçalves da Gardinassi, Luiz Gustavo Araújo |
dc.subject.por.fl_str_mv |
Adenovírus humano Alo-TCPH Imunoinformática Proteína hexon Viremia |
topic |
Adenovírus humano Alo-TCPH Imunoinformática Proteína hexon Viremia Human adenovirus Allo-TCPH Immunoinformatics Hexon protein viremia CIENCIAS BIOLOGICAS::MICROBIOLOGIA::MICROBIOLOGIA APLICADA |
dc.subject.eng.fl_str_mv |
Human adenovirus Allo-TCPH Immunoinformatics Hexon protein viremia |
dc.subject.cnpq.fl_str_mv |
CIENCIAS BIOLOGICAS::MICROBIOLOGIA::MICROBIOLOGIA APLICADA |
description |
Human Adenoviruses (HAdVs) are important infectious agents associated with high incidence, morbidity and mortality in immunocompromised patients, such as those undergoing allogeneic hematopoietic progenitor cell transplantation (allo-TCPH). HAdVs belong to the family Adenoviridae, genus Mastadenovirus, and further classified into seven species (A-G) and 103 genotypes, characterized so far. The HAdV capsid consists mainly of the hexon protein, which has four highly conserved regions (CR1 - 4) that are known for their immunogenic potential, being one of the main targets of the T and B cell-mediated anti-HAdV immune response. The aim of the present study was to perform the mapping of potentially immunogenic epitopes, located in the HAdV hexon CRs and to evaluate the HAdV infection in patients undergoing allo-TCPH. To this end, predictions of T and B cell epitopes and IFN-γ induction were performed, considering 101 HAdV genotypes with sequences available in databases. The most conserved and best classified epitopes were then selected by the prediction programs to perform the molecular docking analysis with HLA alleles of the study population, consisting of nine adult patients undergoing allo-TCPH. It was also carried out the HAdV research by TaqMan real-time polymerase chain reaction (qPCR) in the patient's serum samples. As a result, regions containing overlapping T and B cell epitopes were obtained and, based on immunoinformatics analysis (prediction and molecular docking), two peptides with high conservation and immunogenic potential were designed. Nine patients were positive for HAdV by qPCR TaqMan, with the average viral load found in the serum samples of the study population being 6.71x1011 CG / mL. The genomic sequencing of the positive samples returned sequences that showed 100% similarity with sequences of the HAdV C hexon protein, deposited in a database. The present study allowed the mapping of the main immunogenic regions located in the CRs of the HAdV hexon, as well as the construction of two peptides that will be used in future studies to evaluate the immune response of patients undergoing allo-TCPH, participating in the present study. |
publishDate |
2020 |
dc.date.accessioned.fl_str_mv |
2020-09-04T12:14:48Z |
dc.date.available.fl_str_mv |
2020-09-04T12:14:48Z |
dc.date.issued.fl_str_mv |
2020-03-17 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
ANJOS, D. C. C. Mapeamento imunoinformático de regiões conservadas da proteína hexon de adenovírus humano. 2020. 89 f. Dissertação (Mestrado em Biologia da Relação Parasito-Hospedeiro) - Universidade Federal de Goiás, Goiânia, 2020. |
dc.identifier.uri.fl_str_mv |
http://repositorio.bc.ufg.br/tede/handle/tede/10560 |
dc.identifier.dark.fl_str_mv |
ark:/38995/0013000005xp1 |
identifier_str_mv |
ANJOS, D. C. C. Mapeamento imunoinformático de regiões conservadas da proteína hexon de adenovírus humano. 2020. 89 f. Dissertação (Mestrado em Biologia da Relação Parasito-Hospedeiro) - Universidade Federal de Goiás, Goiânia, 2020. ark:/38995/0013000005xp1 |
url |
http://repositorio.bc.ufg.br/tede/handle/tede/10560 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.relation.program.fl_str_mv |
15 |
dc.relation.confidence.fl_str_mv |
500 500 500 500 |
dc.relation.department.fl_str_mv |
29 |
dc.relation.cnpq.fl_str_mv |
874 |
dc.relation.sponsorship.fl_str_mv |
3 |
dc.rights.driver.fl_str_mv |
Attribution-NonCommercial-NoDerivs 3.0 Brazil http://creativecommons.org/licenses/by-nc-nd/3.0/br/ info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Attribution-NonCommercial-NoDerivs 3.0 Brazil http://creativecommons.org/licenses/by-nc-nd/3.0/br/ |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Universidade Federal de Goiás |
dc.publisher.program.fl_str_mv |
Programa de Pós-graduação em Biologia da Relação Parasito-Hospedeiro (IPTSP) |
dc.publisher.initials.fl_str_mv |
UFG |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
Instituto de Patologia Tropical e Saúde Pública - IPTSP (RG) |
publisher.none.fl_str_mv |
Universidade Federal de Goiás |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UFG instname:Universidade Federal de Goiás (UFG) instacron:UFG |
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Universidade Federal de Goiás (UFG) |
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UFG |
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UFG |
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