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Doctoral Thesis
DOI
https://doi.org/10.11606/T.42.2023.tde-17062024-112631
Document
Author
Full name
Shahab Zaki Pour
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2023
Supervisor
Committee
Zanotto, Paolo Marinho de Andrade (President)
Araujo, Jansen de
Briones, Marcelo Ribeiro da Silva
Hashimoto, Ronaldo Fumio
Title in Portuguese
Análise do perfil de expressão gênica no fígado post mortem em pacientes infectados contra cepas vacinais e silvestres do vírus da febre amarela (YFV)
Keywords in Portuguese
Bulk RNA-Seq
Regulação de expressão gênica
RNA-Seq
Surtos no Brasil
Transcriptoma
Transcriptoma de tecidos
Virus de febre amarela
Abstract in Portuguese
A febre amarela é um vírus de RNA transmitido por mosquitos que pertence ao gênero Flavivírus. É responsável por vários surtos nas América, África e Europa a partir de meados do século XVII. A WHO estima aproximadamente 200.000 casos de doença clínica da febre amarela e 30.000 mortes a cada ano. O Brasil sofreu surtos de YFV desde dezembro de 2016, após a última grande epidemia em 1935-1940. Casos esporádicos foram notificados em estados endêmicos, como os estados da Amazônia, com incursões no Sudeste (Minas Gerais e São Paulo em 2002 e 2008, respectivamente, e Sul (Paraná e Rio Grande do Sul em 2008). Desde primeiro de dezembro de 2016 a 8 de maio 2018, 2050 casos foram confirmados, incluindo 681 mortes com fatalidade de 33,2%, enquanto outros 1300 ainda estão sob investigação. A vacina YFV foi desenvolvida pela primeira vez na década de 1930 devido ao sucesso na atenuação da cepa Asibi. A variante atenuada 17DD é utilizado no Brasil para a fabricação da vacina atenuada YFV Embora a vacina forneça proteção imunológica eficaz e duradoura, causa condições adversas leves, incluindo reações local da injeção, como (inchaço, vermelhidão, dor, inchaço, inchaço e sensibilidade), bem como febre, erupção cutânea, sintomas semelhantes aos da gripe, dor de cabeça ou mal-estar geral. No entanto, reações adversas graves acontecem em uma pequena fração da população vacinada, incluindo doença neurológica associada à vacina e doença viscerotrópica associada à vacina. Neste estudo analizamos o transcriptoma dos casos fatais de YFV durante o surto urbano de 2018 na Região Metropolitana de São Paulo (RMSP). Identificamos 4.101 DEGs (genes diferencialmente expressos) entre os grupos silvestre e Vacina, 2.240 DEGS entre os grupos silvestre e Controle e 4.044 DEGs ao comparar o grupo de Vacina com o grupo Controle. Esses DEGs foram analisados para detectar o enriquecimento de categorias de ontologia genética (GO) ou enciclopédia de Kyoto de vias de genes e genomas (KEGG). Este estudo elucida vias e genes envolvidos nessa patogenicidade.
Title in English
Comparative post-mortem liver-specific gene expression and transcriptome response in wild-type and vaccine adverse reactions of yellow fever
Keywords in English
Brazil outbreak
Bulk RNA-Seq
Differential gene expression
RNA-Seq
Tissue-specific transcriptome
Transcriptome
Yellow Fever Virus
Abstract in English
Yellow Fever is a mosquito-borne RNA virus that belongs to the genus Flavivirus. It was responsible for the numerous epidemics throughout America, Africa, and Europe since the mid-1600s. The WHO estimates approximately 200,000 cases of yellow fever clinical disease and 30,000 deaths each year. Brazil has experienced a YFV outbreak since December 2016 after the last major epidemic in 1935-1940. Sporadic cases were reported from endemic states such as the Amazonia states with some invasion in the Southeast (Minas Gerais and São Paulo in 2002 and 2008 respectively, and South (Paraná and the Rio Grande do Sul in 2008). From 1 December 2016 to 8 May 2018, 2050 cases were confirmed, including 681 deaths with a fatality of 33.2%, while a further 1300 cases are still under investigation. YFV vaccine was first developed in the 1930s due to the success in attenuation of the Asibi 17D strain. The attenuated variant 17DD is being used in Brazil for the manufacturing of the YFV attenuated vaccine. Although the vaccine imparts long-lasting and efficacious immune protection, it causes mild adverse reactions, including injection site reactions such as (swelling, redness, pain, soreness, aches, or a lump and tenderness), as well as, fever, rash, flu-like symptoms, headache, or general ill feeling (malaise). Nevertheless, severe adverse reactions happen to a small fraction of the vaccinated population, including vaccine-associated neurologic disease and vaccine-associated viscerotropic disease were reported. In this study, we conduct the transcriptome of eleven fatal cases of YFV during the 2018 urban outbreak in the metropolitan region of São Paulo (MRSP). We identified 4101 DEGs (differentially expressed genes) between the Sylvatic and Vaccine groups, 2240 DEGs between the Sylvatic and Control groups, and 4044 DEGs when comparing the Vaccine group to the control group. These DEGs have been analyzed to detect the enrichment of Gene Ontology (GO) categories or Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. this study elucidates the pathways and genes involved in this pathogenicity.
 
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Release Date
2026-06-17
Publishing Date
2024-06-19
 
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