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Stability of the HTLV-1 glycoprotein 46 (gp46) gene in an endemic region of the Brazilian Amazon and the presence of a significant mutation (N93D) in symptomatic patients
BACKGROUND: The human T-lymphotropic virus type 1 (HTLV-1) affects 2–5 million people worldwide, and is associated with a number of degenerative and infectious diseases. The Envelope glycoproteins (gp) are highly conserved among the different HTLV-1 isolates, although nucleotide substitutions in the...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5930498/ https://www.ncbi.nlm.nih.gov/pubmed/29716616 http://dx.doi.org/10.1186/s12985-018-0984-9 |
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author | Socorro de Almeida Viana, Maria de Nazaré do Santos Nobre, Akim Felipe Costa Jr, Edivaldo Silva, Ingrid Christiane Pinheiro, Bruna Teles Pereira, Cássia Cristine Costa de Souza Canto Ferreira, Louise de Almeida, Danilo Souza de Araújo, Marcos William Leão da Silva Borges, Mariza da Costa, Carlos Araujo Ishikawa, Edna Aoba Yassui Ferrari, Stephen Francis Silva de Sousa, Maísa |
author_facet | Socorro de Almeida Viana, Maria de Nazaré do Santos Nobre, Akim Felipe Costa Jr, Edivaldo Silva, Ingrid Christiane Pinheiro, Bruna Teles Pereira, Cássia Cristine Costa de Souza Canto Ferreira, Louise de Almeida, Danilo Souza de Araújo, Marcos William Leão da Silva Borges, Mariza da Costa, Carlos Araujo Ishikawa, Edna Aoba Yassui Ferrari, Stephen Francis Silva de Sousa, Maísa |
author_sort | Socorro de Almeida Viana, Maria de Nazaré do |
collection | PubMed |
description | BACKGROUND: The human T-lymphotropic virus type 1 (HTLV-1) affects 2–5 million people worldwide, and is associated with a number of degenerative and infectious diseases. The Envelope glycoproteins (gp) are highly conserved among the different HTLV-1 isolates, although nucleotide substitutions in the region that codifies these proteins may influence both the infectivity and the replication of the virus. The gp46 gene has functional domains which have been associated with the inhibition of the formation of the syncytium, cell-cell transmission, and the production of antibodies. The present study investigated the genetic stability of the gp46 gene of HTLV-1 in an endemic region of Brazilian Amazonia. METHODS: Index case (IC - a sample of a given family group) carriers of HTLV-1 were investigated in the metropolitan region of Belém (Pará, Brazil) between January 2010 (registered retrospectively) and December 2015. The sequences that codify the gp46 were amplified by PCR, purified and sequenced (MF084788–MF084825). The gene was characterized using bioinformatics and Bayesian Inference. RESULTS: The 40 patients analyzed had a mean age of 45.2 years and 70% presented some type of symptom, with a predominance of pain and sensitivity, dysautonomia, and motor disorders. All patients presented the aA (Transcontinental Cosmopolitan) genotype, with an extremely low mutation rate, which is characteristic of the codifying region (aA – 1.83 × 10–(4) mutations per site per year). The gp46 gene had a nucleotide diversity of between 0.00% and 2.0%. Amino acid mutations were present in 66.6% of the samples of individuals with signs/symptoms or diseases associated with HTLV-1 (p = 0.0091). Of the three most frequent mutations, the previously undescribed N93D mutant was invariably associated with symptomatic cases. CONCLUSIONS: The aA HTLV-1 subtype is predominant in the metropolitan region of Belém and presented a high degree of genetic stability in the codifying region. The rare N93D amino acid mutation may be associated with the clinical manifestations of this viral infection. IMPORTANCE: Little is known of the phylogeny of HTLV-1 in the endemic region of Brazilian Amazonia, and few complete gene sequences are available for the gp46 glycoprotein from the local population. The nucleotide sequences of the viral gp46 gene recorded in the present study confirmed the genetic stability of the region, and pointed to a homogeneous viral group, with local geographic characteristics. Further research will be necessary to more fully understand the molecular diversity of this protein, given the potential of this codifying region as a model for an effective HTLV-1 vaccine. The identification of a rare mutation (N93D), present only in symptomatic patients, should also be investigated further as a potential clinical marker. TRIAL REGISTRATION: ISRCTN 12345678, registered 28 September 2014. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12985-018-0984-9) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5930498 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-59304982018-05-09 Stability of the HTLV-1 glycoprotein 46 (gp46) gene in an endemic region of the Brazilian Amazon and the presence of a significant mutation (N93D) in symptomatic patients Socorro de Almeida Viana, Maria de Nazaré do Santos Nobre, Akim Felipe Costa Jr, Edivaldo Silva, Ingrid Christiane Pinheiro, Bruna Teles Pereira, Cássia Cristine Costa de Souza Canto Ferreira, Louise de Almeida, Danilo Souza de Araújo, Marcos William Leão da Silva Borges, Mariza da Costa, Carlos Araujo Ishikawa, Edna Aoba Yassui Ferrari, Stephen Francis Silva de Sousa, Maísa Virol J Research BACKGROUND: The human T-lymphotropic virus type 1 (HTLV-1) affects 2–5 million people worldwide, and is associated with a number of degenerative and infectious diseases. The Envelope glycoproteins (gp) are highly conserved among the different HTLV-1 isolates, although nucleotide substitutions in the region that codifies these proteins may influence both the infectivity and the replication of the virus. The gp46 gene has functional domains which have been associated with the inhibition of the formation of the syncytium, cell-cell transmission, and the production of antibodies. The present study investigated the genetic stability of the gp46 gene of HTLV-1 in an endemic region of Brazilian Amazonia. METHODS: Index case (IC - a sample of a given family group) carriers of HTLV-1 were investigated in the metropolitan region of Belém (Pará, Brazil) between January 2010 (registered retrospectively) and December 2015. The sequences that codify the gp46 were amplified by PCR, purified and sequenced (MF084788–MF084825). The gene was characterized using bioinformatics and Bayesian Inference. RESULTS: The 40 patients analyzed had a mean age of 45.2 years and 70% presented some type of symptom, with a predominance of pain and sensitivity, dysautonomia, and motor disorders. All patients presented the aA (Transcontinental Cosmopolitan) genotype, with an extremely low mutation rate, which is characteristic of the codifying region (aA – 1.83 × 10–(4) mutations per site per year). The gp46 gene had a nucleotide diversity of between 0.00% and 2.0%. Amino acid mutations were present in 66.6% of the samples of individuals with signs/symptoms or diseases associated with HTLV-1 (p = 0.0091). Of the three most frequent mutations, the previously undescribed N93D mutant was invariably associated with symptomatic cases. CONCLUSIONS: The aA HTLV-1 subtype is predominant in the metropolitan region of Belém and presented a high degree of genetic stability in the codifying region. The rare N93D amino acid mutation may be associated with the clinical manifestations of this viral infection. IMPORTANCE: Little is known of the phylogeny of HTLV-1 in the endemic region of Brazilian Amazonia, and few complete gene sequences are available for the gp46 glycoprotein from the local population. The nucleotide sequences of the viral gp46 gene recorded in the present study confirmed the genetic stability of the region, and pointed to a homogeneous viral group, with local geographic characteristics. Further research will be necessary to more fully understand the molecular diversity of this protein, given the potential of this codifying region as a model for an effective HTLV-1 vaccine. The identification of a rare mutation (N93D), present only in symptomatic patients, should also be investigated further as a potential clinical marker. TRIAL REGISTRATION: ISRCTN 12345678, registered 28 September 2014. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12985-018-0984-9) contains supplementary material, which is available to authorized users. BioMed Central 2018-05-02 /pmc/articles/PMC5930498/ /pubmed/29716616 http://dx.doi.org/10.1186/s12985-018-0984-9 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Socorro de Almeida Viana, Maria de Nazaré do Santos Nobre, Akim Felipe Costa Jr, Edivaldo Silva, Ingrid Christiane Pinheiro, Bruna Teles Pereira, Cássia Cristine Costa de Souza Canto Ferreira, Louise de Almeida, Danilo Souza de Araújo, Marcos William Leão da Silva Borges, Mariza da Costa, Carlos Araujo Ishikawa, Edna Aoba Yassui Ferrari, Stephen Francis Silva de Sousa, Maísa Stability of the HTLV-1 glycoprotein 46 (gp46) gene in an endemic region of the Brazilian Amazon and the presence of a significant mutation (N93D) in symptomatic patients |
title | Stability of the HTLV-1 glycoprotein 46 (gp46) gene in an endemic region of the Brazilian Amazon and the presence of a significant mutation (N93D) in symptomatic patients |
title_full | Stability of the HTLV-1 glycoprotein 46 (gp46) gene in an endemic region of the Brazilian Amazon and the presence of a significant mutation (N93D) in symptomatic patients |
title_fullStr | Stability of the HTLV-1 glycoprotein 46 (gp46) gene in an endemic region of the Brazilian Amazon and the presence of a significant mutation (N93D) in symptomatic patients |
title_full_unstemmed | Stability of the HTLV-1 glycoprotein 46 (gp46) gene in an endemic region of the Brazilian Amazon and the presence of a significant mutation (N93D) in symptomatic patients |
title_short | Stability of the HTLV-1 glycoprotein 46 (gp46) gene in an endemic region of the Brazilian Amazon and the presence of a significant mutation (N93D) in symptomatic patients |
title_sort | stability of the htlv-1 glycoprotein 46 (gp46) gene in an endemic region of the brazilian amazon and the presence of a significant mutation (n93d) in symptomatic patients |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5930498/ https://www.ncbi.nlm.nih.gov/pubmed/29716616 http://dx.doi.org/10.1186/s12985-018-0984-9 |
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