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Doctoral Thesis
DOI
https://doi.org/10.11606/T.9.2013.tde-15012014-143723
Document
Author
Full name
Mariana Cavalheiro Magri
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2013
Supervisor
Committee
Araujo, Adele Caterino de (President)
Casseb, Jorge Simão do Rosário
Granato, Celso Francisco Hernandes
Hirata, Rosario Dominguez Crespo
Levi, José Eduardo
Title in Portuguese
Vírus linfotrópicos de células T humanas dos tipos 1 e 2 (HTLV-1 e HTLV-2). Estudo de segmentos do genoma proviral obtidos de pacientes com HIV/Aids de São Paulo e de Londrina e região
Keywords in Portuguese
Caracterização molecular
Coinfecção HIV-1
Epidemiologia
Vírus linfotrópicos de células T humanas do tipo 1 (HTLV-1)
Vírus linfotrópicos de células T humanas do tipo 2 (HTLV 2)
Abstract in Portuguese
O Brasil é considerado o país com o maior número absoluto de indivíduos infectados pelos vírus linfotrópicos de células T humanas dos tipos 1 e 2 (HTLV-1 e HTLV2), perto de 2,5 milhões; além disso, é também considerado epidêmico para o HIV e, portanto, casos de coinfecção HIV/HTLV são frequentes no país. O presente trabalho efetuou o seqüenciamento das regiões LTR, env e tax do genoma proviral do HTLV-1 e do HTLV-2 isolados das amostras de sangue de pacientes coinfectados pelo HIV-1 de Londrina e região (n=34) e de São Paulo (n=20), para realizar a caracterização molecular e determinar subtipos virais. Foram utilizadas na análise das sequências as ferramentas Sequencher 4.7, BLAST, Genotyping-NCBI, Subtyping-REGA, BioEdit 7.0.5.3, ClustalW, GenBank, PAUP 4.0.b10, Modeltest 3.7, TreeView 1.6.6 e MEGA4. As diversas análises confirmaram como subtipos prevalentes o HTLV-1a, subgrupo Transcontinental A, e o HTLV-2a (variante -2c). Foram detectadas assinaturas moleculares nos isolados do Brasil. Detectou-se o genótipo brasileiro taxA para o HTLV-1 e para o HTLV-2 a Tax longa, a qual é característica da variante HTLV-2c. Houve também a confirmação da troca de aminoácido S1909P no env dos HTLV-2. Especulou-se sobre duas entradas do HTLV-1 no Brasil e sobre a disseminação do HTLV-2c em grupos distintos quanto ao comportamento de risco e região geográfica. O estabelecimento de métodos laboratoriais otimizados para isolados brasileiros de HTLV-1 e HTLV-2 possibilitou melhor compreensão da diversidade genômica e da origem e disseminação dos HTLVs em populações coinfectadas pelo HIV no Brasil.
Title in English
Human T-lymphotropic virus type 1 and 2 (HTLV-1 and HTLV-2). Study on proviral genome segments obtained from patients with HIV/Aids from Sao Paulo and Londrina and vicinities.
Keywords in English
Epidemiology
HIV-1 Coinfection
Human T-lymphotropic virus type 1 (HTLV-1)
Human T-lymphotropic virus type 2 (HTLV-2)
Molecular characterization
Abstract in English
Brazil is considered the country with the major absolute number of individuals infected with human T-lymphotropic virus types 1 and 2 (HTLV-1 and HTLV-2), close to 2,500,000; moreover, it is also considered epidemic for HIV/Aids =and therefore HIV/HTLV coinfection is frequent in the country. This study aimed at sequencing the LTR, env and tax regions of the proviral genome of HTLV-1 and HTLV-2 isolated from blood samples obtained from patients coinfected with HIV-1 from Londrina and vicinities (n=34) and São Paulo (n=20), in order to perform the molecular characterization and viral subtyping. For sequences analysis, several bioinformatics tools were employed: Sequencher 4.7, BLAST, Genotyping-NCBI, Subtyping-REGA, BioEdit 7.0.5.3, ClustalW, GenBank, PAUP 4.0.b10, Modeltest 3.7, TreeView 1.6.6 and MEGA4. The results confirmed as prevalent the HTLV-1a subtype, the Transcontinental subgroup A, and the HTLV-2a (variant-2c). Molecular signatures characteristic of Brazilian isolates were detected: taxA Brazilian genotype in HTLV-1, and the long Tax which is characteristic of the HTLV-2c in HTLV-2. Also, it was confirmed the S1909P amino acid change in the env region of HTLV-2c. It was speculated on two entrances of HTLV-1 in Brazil, and on the spread of HTLV-2c in distinct groups related to risk factors and geographic region. The establishment and optimization of laboratory methods performed in this study allowed to get a better understanding on HTLVs genomic diversity, and to give insights on the origin and spread of HTLVs in populations coinfected with HIV in Brazil.
 
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Publishing Date
2014-03-28
 
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