Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/8767
Title: Molecular characterization of HTLV-1 gp46 glycoprotein from health carriers and HAM/TSP infected individuals.
Authors: Miranda, Aline Cristina Andrade Mota
Barreto, Fernanda Khouri
Amarante, Maria Fernanda de Castro
Batista, Everton da Silva
Cunha, Joana Paixão Monteiro
Vallve, Maria de Lourdes Farre
Castro Filho, Bernardo Galvão
Alcantara, Luiz Carlos Júnior
Affilliation: Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Escola Bahiana de Medicina e Saúde Pública. Salvador, BA, Brasil / Universidade Federal da Bahia. Instituto de Ciências da Saúde. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
Cancer Institute. National Institutes of Health. Bethesda, MD, USA
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Laboratório de Patologia Experimental. Salvador, BA, Brasil
Escola Bahiana de Medicina e Saúde Pública. Salvador, BA, Brasil / Universidade Federal da Bahia. Instituto de Ciências da Saúde. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Laboratório de Patologia Experimental. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Escola Bahiana de Medicina e Saúde Pública. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
Abstract: BACKGROUND: Human T-cell Leukemia Virus type 1 (HTLV-1) is the etiological agent of tropical spastic paraparesis/HTLV-associated myelopathy (HAM/TSP) that can be identified in around 0.25%-3.8% of the infected population. Disease progression can be monitored by the proviral load and may depend on genetic factors, however, it is not well understood why some HTLV-1 infected people develop the disease while others do not. The present study attempts to assess the molecular diversity of gp46 glycoprotein in HAM/TSP patients and Health Carrier (HC) individuals. METHODS: Blood samples were collected from 10 individuals, and DNA was extracted from PBMCs to measure the HTLV-1 proviral load. The gp46 coding sequences were amplified PCR, cloned and sequenced. The molecular characterization was performed using bioinformatics tools. RESULTS: The median HTLV-1 proviral load of HC (n = 5) and HAM/TSP (n = 5) patients was similar (average 316,227 copies/106 PBMCs). The gp46 molecular characterization of 146 clones (70 HC and 76 HAM/TSP) revealed an overall diversity, within HC and HAM/TSP clones, of 0.4% and 0.6%, respectively. Five frequent mutations were detected among groups (HAM/TSP and HC clone sequences). A single amino acid (aa) substitution (S35L) was exclusive for the HC group, and three gp46 substitutions (F14S, N42H, G72S) were exclusive for the HAM/TSP group. The remaining frequent mutation (V247I) was present in both groups (p = 0.0014). The in silico protein analysis revealed that the mutated alleles F14S and N42H represent more hydrophilic and flexible protein domains that are likely to be less antigenic. The Receptor Binding Domain is quite variable in the HAM/TSP group. Two other domains (aa 53-75 and 175-209) that contain multiple linear T-cell epitopes showed genetic diversity in both HAM/TSP and HC groups. Further analysis revealed 27 and 13 T-cell epitopes for class I HLA alleles and class II HLA alleles, when analyzing the entire gp46. CONCLUSIONS: The most common gp46 mutations were not associated clinical status because they were found in only one individual, except for the V247I mutation, that was found at viral clones from HAM/TSP ad HC individuals. Because of this, we cannot associate any of the gp46 found mutations with the clinical profile.
Keywords: HTLV-1
HAM/TSP
Gp46
Mutation
DeCS: Portador Sadio/virologia
Produtos do Gene env/genética
Vírus 1 Linfotrópico T Humano/genética
Paraparesia Espástica Tropical/virologia
Proteínas Oncogênicas de Retroviridae/genética
Adulto
Idoso
Sequência de Aminoácidos
Portador Sadio/imunologia
Epitopos de Linfócito T/química
Produtos do Gene env/química
Feminino
Vírus 1 Linfotrópico T Humano/química
Vírus 1 Linfotrópico T Humano/isolamento & purificação
Humanos
Masculino
Meia-Idade
Dados de Sequência Molecular
Mutação
Paraparesia Espástica Tropical/imunologia
Estrutura Terciária de Proteína
Proteínas Oncogênicas de Retroviridae/imunologia
Issue Date: 2013
Publisher: BioMed Central
Citation: MIRANDA, A. C. A. M. et al. Molecular characterization of HTLV-1 gp46 glycoprotein from health carriers and HAM/TSP infected individuals. Virology Journal, v. 10, p. 75, 2013.
DOI: 10.1186/1743-422X-10-75
ISSN: 1743-422X
Copyright: open access
Appears in Collections:BA - IGM - Artigos de Periódicos

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