Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/8767
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dc.contributor.authorMiranda, Aline Cristina Andrade Mota
dc.contributor.authorBarreto, Fernanda Khouri
dc.contributor.authorAmarante, Maria Fernanda de Castro
dc.contributor.authorBatista, Everton da Silva
dc.contributor.authorCunha, Joana Paixão Monteiro
dc.contributor.authorVallve, Maria de Lourdes Farre
dc.contributor.authorCastro Filho, Bernardo Galvão
dc.contributor.authorAlcantara, Luiz Carlos Júnior
dc.date.accessioned2014-11-07T17:45:32Z
dc.date.available2014-11-07T17:45:32Z
dc.date.issued2013
dc.identifier.citationMIRANDA, 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.
dc.identifier.issn1743-422X
dc.identifier.urihttps://www.arca.fiocruz.br/handle/icict/8767
dc.language.isoeng
dc.publisherBioMed Central
dc.rightsopen access
dc.titleMolecular characterization of HTLV-1 gp46 glycoprotein from health carriers and HAM/TSP infected individuals.
dc.typeArticle
dc.identifier.doi10.1186/1743-422X-10-75
dc.description.abstractenBACKGROUND: 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.
dc.creator.affilliationFundação 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
dc.creator.affilliationFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
dc.creator.affilliationCancer Institute. National Institutes of Health. Bethesda, MD, USA
dc.creator.affilliationFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Laboratório de Patologia Experimental. Salvador, BA, Brasil
dc.creator.affilliationEscola Bahiana de Medicina e Saúde Pública. Salvador, BA, Brasil / Universidade Federal da Bahia. Instituto de Ciências da Saúde. Salvador, BA, Brasil
dc.creator.affilliationFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Laboratório de Patologia Experimental. Salvador, BA, Brasil
dc.creator.affilliationFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Escola Bahiana de Medicina e Saúde Pública. Salvador, BA, Brasil
dc.creator.affilliationFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
dc.subject.enHTLV-1
dc.subject.enHAM/TSP
dc.subject.enGp46
dc.subject.enMutation
dc.subject.decsPortador Sadio/virologia
dc.subject.decsProdutos do Gene env/genética
dc.subject.decsVírus 1 Linfotrópico T Humano/genética
dc.subject.decsParaparesia Espástica Tropical/virologia
dc.subject.decsProteínas Oncogênicas de Retroviridae/genética
dc.subject.decsAdulto
dc.subject.decsIdoso
dc.subject.decsSequência de Aminoácidos
dc.subject.decsPortador Sadio/imunologia
dc.subject.decsEpitopos de Linfócito T/química
dc.subject.decsProdutos do Gene env/química
dc.subject.decsFeminino
dc.subject.decsVírus 1 Linfotrópico T Humano/química
dc.subject.decsVírus 1 Linfotrópico T Humano/isolamento & purificação
dc.subject.decsHumanos
dc.subject.decsMasculino
dc.subject.decsMeia-Idade
dc.subject.decsDados de Sequência Molecular
dc.subject.decsMutação
dc.subject.decsParaparesia Espástica Tropical/imunologia
dc.subject.decsEstrutura Terciária de Proteína
dc.subject.decsProteínas Oncogênicas de Retroviridae/imunologia
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