Please use this identifier to cite or link to this item: http://www.arca.fiocruz.br/handle/icict/13371
Title: Deep Sequencing Analysis of Human T Cell Lymphotropic Virus Type 1 Long Terminal Repeat 5' Region from Patients with Tropical Spastic Paraparesis/Human T Cell Lymphotropic Virus Type 1-Associated Myelopathy and Asymptomatic Carriers.
Authors: Rego, Filipe Ferreira de Almeida
Oliveira, Tulio de
Giovanetti, Marta
Castro Filho, Bernardo Galvão
Gonçalves, Marilda de Souza
Alcantara, Luiz Carlos Júnior
Affilliation: Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Laboratório de Hematologia, Genética e Biologia Computacional. Salvador, BA, Brasil / University of KwaZulu-Natal. Africa Centre for Health and Population Study. KwaZulu-Natal, South Africa / Universidade Católica do Salvador. Salvador, BA, Brasil
University of KwaZulu-Natal. Africa Centre for Health and Population Study. KwaZulu-Natal, South Africa
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Laboratório de Hematologia, Genética e Biologia Computacional. Salvador, BA, Brasil
HTLV Center. Bahia School of Medicine and Public Health. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Laboratório de Hematologia, Genética e Biologia Computacional. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Laboratório de Hematologia, Genética e Biologia Computacional. Salvador, BA, Brasil
Abstract: The aim of this study was to analyze patients by deep sequencing the human T cell lymphotropic virus type 1 (HTLV-1) long terminal repeat (LTR) region in order to determine if minor and/or major mutations in this promoter region might be associated with tropical spastic paraparesis (TSP)/human T cell lymphotropic virus type 1-associated myelopathy (HAM) outcome or proviral load or HTLV-1 expression. This study is a cross-sectional analyze of 29 HTLV-1-infected patients with TSP/HAM or asymptomatic carriers. Proviral DNA from those subjects was submitted to a nested PCR for the HTLV-1 LTR5' region. The HTLV-1 LTR5' purified products were submitted to deep sequencing using the Ion Torrent sequencing technology (Life Technologies, Carlsbad, CA). We found that samples with low proviral load showed more detected minor mutations than the samples with high proviral load. Mutations in 136 positions were found over the 520-bp analyzed fragment of HTLV-1 LTR5' with at least 1% frequency. Eleven mutations were present in the previously determined major transcription factor binding sites (TFBS) and in more than one patient, indicating that there might be a differential HTLV-1 expression comparing individuals or in comparing different cells from the same individual. Three mutations were statistically significant using the Fisher nonparametric test between the groups but were not present in previously determined TFBS (G126C/T, G306C, and C479T). Those mutations that were not present in previously determined TFBS were statistically significant in this study and were most frequent in patients with low proviral load or in asymptomatic carriers. Although those mutations were not present in previously determined TFBS, one of those mutations (G306C/A) was present in an Sp-1 binding site determined by in silico analysis, and its presence abrogated the site for Sp-1 binding and created a new possible ATF binding site.
keywords: Virus Linfotrópico 1
HTLV-1
Paraparesia espástica
Mutações
Mielopatia associada ao HTLV-1
Issue Date: 2016
Publisher: Mary Ann Liebert
Citation: REGO, F. A. F. et al. Deep Sequencing Analysis of Human T Cell Lymphotropic Virus Type 1 Long Terminal Repeat 5' Region from Patients with Tropical Spastic Paraparesis/Human T Cell Lymphotropic Virus Type 1-Associated Myelopathy and Asymptomatic Carriers. AIDS Research Human and Retroviruses, v. 32, n. 3, p. 279-283, 2016.
ISSN: 1931-8405
10.1089/aid.2015.0273
Copyright: open access
Appears in Collections:IGM - Artigos de Periódicos

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