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Doctoral Thesis
DOI
https://doi.org/10.11606/T.10.2014.tde-24072014-103209
Document
Author
Full name
Willian de Oliveira Fahl
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2014
Supervisor
Committee
Brandão, Paulo Eduardo (President)
Gregori, Fabio
Kawai, Juliana Galera Castilho
Mori, Enio
Sakamoto, Sidnei Miyoshi
Title in Portuguese
Marcadores moleculares para a patogenia de vírus da raiva: relação entre períodos de incubação, carga viral e os genes codificadores das proteínas virais P e L
Keywords in Portuguese
Fosfoproteína
Marcadores moleculares
Patogenia
Raiva
RNA polimerase RNA dependente
Abstract in Portuguese
A raiva é uma doença aguda, progressiva e infecciosa do sistema nervoso central de mamíferos, causada pelo vírus da raiva (RABV). Embora possa ser prevenida por vacina, continua sendo um grave problema de saúde pública, além de ser responsável pela morte de seres humanos e muitos outros animais, incluindo os de interesse econômico. Este estudo teve como objetivo avaliar a relação entre polimorfismos dos genes que codificam as proteínas P e L de amostras de RABV pertencentes a variantes antigênicas 2 e 3 e períodos de incubação e títulos em camundongos. Para isso, foram selecionadas amostras isoladas de diferentes reservatórios de raiva de mamíferos das Ordens Carnivora e Chiroptera e amostras de bovinos, de áreas endêmicas para o vírus da raiva. As sequências obtidas foram utilizadas para a construção de árvores filogenéticas para procurar os padrões de segregação de linhagens. Os resultados mostraram que não houve marcadores ou polimorfismos que explicam as variações nos períodos de incubação e de letalidade entre cepas pertencentes a variantes antigênicas 2 e 3. Esta informação pode ser usada para discussões sobre a importância de reservatórios de raiva, a dinâmica do vírus da manutenção e evolução das diferentes formas desta zoonose entre os animais infectados, contribuindo para um estudo mais aprofundado sobre a busca de marcadores moleculares para patogênese.
Title in English
Molecular markers for the pathogenesis of rabies virus: relationship among incubation periods, viral load and the genes encoding the viral P and L proteins
Keywords in English
Molecular markers
Pathogenesis
Phosphoprotein
Rabies
RNA dependent RNA polymerase
Abstract in English
Rabies is an acute, progressive and infectious disease of the central nervous system of mammals, caused by Rabies virus (RABV). Although preventable by vaccine, it remains a serious public health problem, and is responsible for the death of humans and many other animals, including those of economic interest. This study aimed to assess the relationship between polymorphisms in genes encoding the P and L proteins of RABV samples belonging to antigenic variants 2 and 3 and incubation periods and titers in mice. For this, samples isolated from different mammalian rabies reservoirs of the Orders Carnivora and Chiroptera and samples of cattle from endemic areas for rabies virus were selected. The sequences obtained were used to construct phylogenetic trees to search for the segregation patterns of strains. The results showed that there were no markers or polymorphisms that explain variations in incubation periods and lethality amongst strains belonging to antigenic variants 2 and 3. This information might be used for discussions about the importance of rabies reservoirs, the dynamics of the virus maintenance and evolution of the different forms of this zoonotic disease among infected animals, contributing to further study about the search for molecular markers for pathogenesis.
 
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Publishing Date
2014-08-28
 
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