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Doctoral Thesis
DOI
10.11606/T.95.2014.tde-21012015-165014
Document
Author
Full name
Caio César de Melo Freire
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2014
Supervisor
Committee
Zanotto, Paolo Marinho de Andrade (President)
Brandão, Paulo Eduardo
Matioli, Sergio Russo
Nakano, Fábio
Souza, Robson Francisco de
Title in Portuguese
Caracterização de processos evolutivos de vírus de RNA a partir de padrões deixados nas filogenias virais
Keywords in Portuguese
bioinformática
evolução de vírus
filogenias
genomas de RNA
rearranjos
recombinação
Abstract in Portuguese
No presente trabalho, investigamos a filodinâmica de três modelos virais diferentes, utilizando técnicas baseadas em verossimilhança e inferência bayesiana. Dois desses são flavivírus com genoma de RNA fita simples e senso positivo. O terceiro é um bunyavírus com genoma tri-segmentado de RNA fita simples com senso negativo. Estes diferentes modelos permitiram estudar diferentes mecanismos promotores de diversidade viral, reagrupamento de segmentos genômicos (shift) e mutação (drift), que atuam em diferentes granularidades. Descrevemos pela primeira vez o espalhamento geográfico das linhagens de vírus Zika (ZIKV) em um nível continental, assim como ocorrência de recombinação e associação entre padrões de glicosilação e vetores. Para o flavivírus da encefalite transmitida por carrapatos (TBEV), investigamos seu espalhamento e encontramos evidências que corroboram a hipótese de circulação viral restrita a focos na Europa central. As análises sobre o vírus da Febre da Grande Fenda Africana (RVFV) apontaram a ocorrência de reagrupamento de segmentos genômicos e também ajudaram a elucidar sua dispersão do leste do continente africano para o oeste, encontrando-se diversas introduções no Senegal e Mauritânia. Aparentemente, este vírus teve a entrada facilitada nesses países por uma região que funciona como um centro de dispersão (hub) por ser encontro de rotas migratórias de animais. Ademais, investigamos a ocorrência de rearranjos de segmentos genômicos de RVFV e também estudamos as diferenças nas dinâmicas evolutivas de cada segmento.
Title in English
Characterization of evolutionary process of RNA viruses from patterns in viral phylogenies
Keywords in English
bioinformatics
molecular evolution
reassortment
recombination
RNA virus
viral evolution
Abstract in English
In this study, we investigated the phylodynamics of three different viral models, using techniques based on maximum likelihood and Bayesian inference methods. Two of these viruses are flaviviruses, whose genomes are formed by a single-stranded positive-sense RNA molecule. The third is a Bunyavirus with tri-segmented single-stranded RNA genome with negative sense. These different models allowed us to investigate two different mechanisms to promote viral diversity, (i) recombination of genomic segments ("shift") and (ii) mutation ("drift"), therefore exploring different levels of granularity of evolutionary process. We described for the first time the geographic spread of Zika virus (ZIKV) strains in a continental level, as well as, the occurrence of recombination and association between glycosylation patterns and vectors. For the other Flavivirus, tick-borne encephalitis virus (TBEV), we investigated its spreading and found evidences to support the hypothesis that viral circulation is very constrained by the foci in central Europe. The analyses about the Rift Valley Fever Virus (RVFV) revealed the occurrence of reassortment of genomic segments and their dispersal from eastern Africa to the west, with several introductions to Senegal and Mauritania. Apparently, the entry of RVFV in these countries was facilitated by the region of Kedougou, where several migratory routes of animals converge. This place maybe works as a hub to spread RVFV for West Africa. Moreover, we also investigated the differences in evolutionary dynamics of each genomic segment of RVFV.
 
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Publishing Date
2015-01-26
 
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