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1.
J Neurovirol ; 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38653958

RESUMO

Human T-lymphotropic virus type 1 (HTLV-1) is classically associated with the HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), although the mechanisms of this neurological disorder remain unclear. In addition, some patients who develop "minor" neurological signs that do not meet diagnostic criteria for HAM/TSP are classified as asymptomatic carriers. This study aims to demonstrate the neurological symptoms of Brazilian patients living with HTLV-1 classified as not-HAM.TSP. This observational study evaluated patients treated in an HTLV reference center in Bahia, Brazil, between February 2022 and July 2023. The data were obtained through the analysis of medical records and neurological consultation. Those individuals classified as HAM/ TSP were excluded from this study. 74 patients were submitted to a careful neurological evaluation: 23 HAM/TSP, 22 were classified with intermediate syndrome (IS), and 29 were oligosymptomatic. Self-reported symptoms were significantly more common in the IS group, including urinary symptoms such as nocturia, urgency, incontinence, dysuria, weakness, paresthesia, lumbar pain, xerostomia, and xerophthalmia. Physical examination findings consistent with reduced vibratory and tactile sensitivity were more common in the IS group (p = 0.017 and p = 0.013). Alterations in the V and VIII cranial nerves were present in both groups. HTLV-1 can lead to the development of important neurological signs and symptoms in apparently asymptomatic individuals. This data highlights the need for more research into the neurological aspects of HTLV-1 infection and emphasizes the importance of early diagnosis, treatment, and support for individuals living with this virus.

2.
Epidemiol Serv Saude ; 32(2): e2022614, 2023.
Artigo em Inglês, Português | MEDLINE | ID: mdl-37610938

RESUMO

MAIN RESULTS: Technology transfer can take place at large events, as long as safety protocols are strictly enforced. It is important to disseminate, at these events, the concepts of the Responsible Research and Innovation (RRI). Implications for services: Face-to-face training course is fundamental for training public health professionals. Technology transfer between research institutions and health services results in updating and improving health system performance. PERSPECTIVES: Based on the success of the reported technology transfer, a new module will be incorporated into the next edition of VEME (Panama 2022), entitled Virus Evolution to Public Health Policy Makers. The objective of this report was to describe the first face-to-face course aimed at training public health professionals in performing real-time genomic surveillance during the pandemic period. Experience report on a theoretical-practical course focusing on genomic research and surveillance, including mobile sequencing technologies, bioinformatics, phylogenetics and epidemiological modeling. There were 162 participants in the event and it was the first major face-to-face training course conducted during the COVID-19 epidemic in Brazil. No cases of SARS-CoV-2 infection was detected among the participants at the end of the event, suggesting the safety and effectiveness of all safety measures adopted. The results of this experience suggest that it is possible to conduct professional training safely during pandemics, as long as all safety protocols are followed.


Assuntos
COVID-19 , Educação Profissional em Saúde Pública , Transferência de Tecnologia , Humanos , Brasil/epidemiologia , COVID-19/epidemiologia , Pandemias , SARS-CoV-2 , Educação Profissional em Saúde Pública/métodos
3.
Viruses ; 15(3)2023 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-36992487

RESUMO

Aedes aegypti and Aedes albopictus are the vectors of important arboviruses: dengue fever, chikungunya, Zika, and yellow fever. Female mosquitoes acquire arboviruses by feeding on the infected host blood, thus being able to transmit it to their offspring. The intrinsic ability of a vector to infect itself and transmit a pathogen is known as vector competence. Several factors influence the susceptibility of these females to be infected by these arboviruses, such as the activation of the innate immune system through the Toll, immunodeficiency (Imd), JAK-STAT pathways, and the interference of specific antiviral response pathways of RNAi. It is also believed that the presence of non-pathogenic microorganisms in the microbiota of these arthropods could influence this immune response, as it provides a baseline activation of the innate immune system, which may generate resistance against arboviruses. In addition, this microbiome has direct action against arboviruses, mainly due to the ability of Wolbachia spp. to block viral genome replication, added to the competition for resources within the mosquito organism. Despite major advances in the area, studies are still needed to evaluate the microbiota profiles of Aedes spp. and their vector competence, as well as further exploration of the individual roles of microbiome components in activating the innate immune system.


Assuntos
Aedes , Arbovírus , Febre de Chikungunya , Microbiota , Febre Amarela , Infecção por Zika virus , Zika virus , Animais , Feminino , Humanos , Arbovírus/genética
4.
Front Immunol ; 14: 1073779, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36860854

RESUMO

Introduction: The Human T-lymphotropic virus type 1 (HTLV-1) was the first described human retrovirus. It is currently estimated that around 5 to 10 million people worldwide are infected with this virus. Despite its high prevalence, there is still no preventive vaccine against the HTLV-1 infection. It is known that vaccine development and large-scale immunization play an important role in global public health. To understand the advances in this field we performed a systematic review regarding the current progress in the development of a preventive vaccine against the HTLV-1 infection. Methods: This review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA®) guidelines and was registered at the International Prospective Register of Systematic Reviews (PROSPERO). The search for articles was performed in PubMed, Lilacs, Embase and SciELO databases. From the 2,485 articles identified, 25 were selected according to the inclusion and exclusion criteria. Results: The analysis of these articles indicated that potential vaccine designs in development are available, although there is still a paucity of studies in the human clinical trial phase. Discussion: Although HTLV-1 was discovered almost 40 years ago, it remains a great challenge and a worldwide neglected threat. The scarcity of funding contributes decisively to the inconclusiveness of the vaccine development. The data summarized here intends to highlight the necessity to improve the current knowledge of this neglected retrovirus, encouraging for more studies on vaccine development aiming the to eliminate this human threat. Systematic review registration: https://www.crd.york.ac.uk/prospero, identifier (CRD42021270412).


Assuntos
Infecções por HTLV-I , Vírus Linfotrópico T Tipo 1 Humano , Humanos , Infecções por HTLV-I/prevenção & controle , Bases de Dados Factuais , Imunização , Desenvolvimento de Vacinas
5.
Epidemiol. serv. saúde ; 32(2): e2022614, 2023. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1506220

RESUMO

Abstract The objective of this report was to describe the first face-to-face course aimed at training public health professionals in performing real-time genomic surveillance during the pandemic period. Experience report on a theoretical-practical course focusing on genomic research and surveillance, including mobile sequencing technologies, bioinformatics, phylogenetics and epidemiological modeling. There were 162 participants in the event and it was the first major face-to-face training course conducted during the COVID-19 epidemic in Brazil. No cases of SARS-CoV-2 infection was detected among the participants at the end of the event, suggesting the safety and effectiveness of all safety measures adopted. The results of this experience suggest that it is possible to conduct professional training safely during pandemics, as long as all safety protocols are followed.


Resumen Este estudio tuvo como objetivo describir el primer curso presencial para capacitar a los profesionales de la salud pública para llevar a cabo la vigilancia genómica en tiempo real durante los períodos de pandemia. Este es un informe de experiencia en un curso teórico-práctico centrado en la investigación y vigilancia genómica, que incluye secuenciación móvil, bioinformática, filogenética y tecnologías de modelado epidemiológico. Este evento contó con la asistencia de 162 participantes y fue la primera gran capacitación presencial realizada durante la epidemia de COVID-19 en Brasil. No se detectó infección por SARS-CoV-2 al final del evento en ningún participante, lo que sugiere la seguridad y efectividad de todas las medidas de seguridad adoptadas. Por lo tanto, los resultados del evento sugieren que es posible realizar entrenamientos profesionales de manera segura durante pandemias, siempre y cuando se sigan todos los protocolos de seguridad.


Resumo O relato descrebeu o primeiro curso presencial visando capacitar profissionais de saúde pública na realização de vigilância genômica em tempo real, durante períodos pandêmicos. Relato de experiência sobre um curso teórico-prático com foco em pesquisa e vigilância genômica, incluindo tecnologias de sequenciamento móvel, bioinformática, filogenética e modelagem epidemiológica. O evento contou com 162 participantes e foi o primeiro grande treinamento presencial realizado durante a epidemia de covid-19 no Brasil. Não foi detectada infecção pelo SARS-CoV-2 ao final do evento em nenhum participante, sugerindo a segurança e efetividade de todas as medidas de segurança adotadas. Os resultados do evento sugerem que é possível executar capacitação profissional com segurança durante pandemias, desde que seguidos todos os protocolos de segurança.

6.
Viruses ; 16(1)2023 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-38257724

RESUMO

The emergence and continued geographic expansion of arboviruses and the growing number of infected people have highlighted the need to develop and improve multiplex methods for rapid and specific detection of pathogens. Sequencing technologies are promising tools that can help in the laboratory diagnosis of conditions that share common symptoms, such as pathologies caused by emerging arboviruses. In this study, we integrated nanopore sequencing and the advantages of reverse transcription polymerase chain reaction (RT-PCR) to develop a multiplex RT-PCR protocol for the detection of Chikungunya virus (CHIKV) and several orthoflaviviruses (such as dengue (Orthoflavivirus dengue), Zika (Orthoflavivirus zikaense), yellow fever (Orthoflavivirus flavi), and West Nile (Orthoflavivirus nilense) viruses) in a single reaction, which provides data for sequence-based differentiation of arbovirus lineages.


Assuntos
Arbovírus , Vírus Chikungunya , Dengue , Sequenciamento por Nanoporos , Infecção por Zika virus , Zika virus , Humanos , Arbovírus/genética , Vírus Chikungunya/genética , Reação em Cadeia da Polimerase Multiplex , Zika virus/genética
7.
Rev. baiana saúde pública ; 45(4): 81-96, 20211212.
Artigo em Português | LILACS | ID: biblio-1414889

RESUMO

O vírus linfotrópico T humano tipo 1 (HTLV-1) foi o primeiro retrovírus humano descoberto, descrito pela primeira vez há 41 anos. Esse retrovírus está associado ao desenvolvimento de duas doenças graves: a leucemia/linfoma de células T do adulto (ATLL) e a mielopatia associada ao HTLV-1/paraparesia espástica tropical (HAM/TSP). Este trabalho teve como objetivo analisar as atualizações sobre o HTLV-1, destacando os aspectos clínicos, os avanços e as limitações no tratamento e na prevenção da infecção pelo HTLV-1. Para isso, foi realizada uma revisão integrativa, por meio de coleta de dados nas plataformas PubMed, LILACS e SciELO, entre março e abril de 2021. Foram incluídos 61 artigos de diferentes países. O Brasil foi o país com maior número de publicações na área: 12. Os resultados obtidos mostram que existem avanços importantes no que diz respeito ao tratamento e à prevenção da infecção pelo HTLV-1. No entanto, a falta de estudos específicos sobre o vírus, que abordem os aspectos clínicos da infecção, foi um fator limitante para este estudo, o que reforça a necessidade de investimento em novas pesquisas sobre o tema.


The Human T-lymphotropic Virus 1 (HTLV-1) was the first human retrovirus discovered, described for the first time 41 years ago. This retrovirus is associated with the development of two serious diseases: adult T-cell leukemia/lymphoma (ATLL) and tropical spastic paraparesis/HTLV-1-associated myelopathy (HAM/TSP). This study aimed to analyze the updates about HTLV-1, highlighting the clinical aspects, advances, and limitations in the treatment and prevention of HTVL-1 infection. To this end, an integrative review was carried out, with data collection on PubMed, LILACS, and SciELO platforms, between March and April 2021. A total of 61 articles from different countries were included. Brazil was the country with the largest number of publications in the area: 12. The results showed effective advances regarding treating and preventing HTLV-1 infection. However, the lack of specific studies about the virus, which address the clinical aspects of the infection, was a limiting factor for this study, which reinforces the need for investment in new research about this topic.


El virus linfotrópico T tipo 1 humano (HTLV-1) fue el primer retrovirus humano descubierto y se describió por primera vez hace 41 años. Este retrovirus está asociado con el desarrollo de dos enfermedades graves: leucemia/linfoma de células T del adulto (ATLL) e mielopatía asociada a HTLV-1/paraparesia espástica tropical (HAM/TSP). Este estudio tuvo como objetivo analizar las actualizaciones sobre HTLV-1, destacando los aspectos clínicos, los avances y limitaciones en el tratamiento y prevención de la infección por HTLV-1. Para ello, se realizó una revisión integradora, a través de la recolección de datos en las plataformas PubMed, LILACS y SciELO entre marzo y abril de 2021. Se incluyeron 61 artículos de diferentes países. Brasil fue el país con mayor número de publicaciones en el área: 12. Los resultados obtenidos muestran que existen avances efectivos en cuanto al tratamiento y prevención de la infección por HTLV-1. Sin embargo, la falta de estudios específicos sobre el virus que aborden los aspectos clínicos de la infección fue un factor limitante para el presente estudio, lo que refuerza la necesidad de invertir en nuevas investigaciones sobre este virus.


Assuntos
Vírus Linfotrópico T Tipo 1 Humano , Infecções por Deltaretrovirus , Retrovirus Endógenos
8.
Arch Virol ; 166(11): 3037-3048, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34415436

RESUMO

Human T-lymphotropic virus type 1 (HTLV-1) was the first human retrovirus described. The viral factors involved in the different clinical manifestations of infected individuals are still unknown, and in this sense, sequencing technologies can support viral genome studies, contributing to a better understanding of infection outcome. Currently, several sequencing technologies are available with different approaches. To understand the methodological advances in the HTLV-1 field, it is necessary to organize a synthesis by a rigorous review. This systematic literature review describes different technologies used to generate HTLV-1 sequences. The review follows the PRISMA guidelines, and the search for articles was performed in PubMed, Lilacs, Embase, and SciELO databases. From the 574 articles found in search, 62 were selected. The articles showed that, even with the emergence of new sequencing technologies, the traditional Sanger method continues to be the most commonly used methodology for generating HTLV-1 genome sequences. There are many questions that remain unanswered in the field of HTLV-1 research, and this reflects on the small number of studies using next-generation sequencing technologies, which could help address these gaps. The data compiled and analyzed here can help research on HTLV-1, assisting in the choice of sequencing technologies.


Assuntos
Vírus Linfotrópico T Tipo 1 Humano/genética , Análise de Sequência de RNA/métodos , Brasil , Genoma Viral , Infecções por HTLV-I/virologia , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos
10.
J Med Virol ; 93(11): 6418-6423, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-33835501

RESUMO

The human T-cell lymphotropic virus type-1 (HTLV-1) is associated with severe pathologies, such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), adult T-cell leukemia-lymphoma (ATLL), and infective dermatitis associated with the HTLV-1 (IDH). Interestingly, HTLV-1 infection does not necessarily imply the development of pathological processes and it is unknown why some patients remain asymptomatic carriers (AC). Despite some mutations in the HTLV-1 genome appear to influence the outcome of HTLV-1, there are few studies that characterize molecularly the hbz region. This study aimed to perform the molecular characterization of hbz gene isolated from patients with different clinical outcomes. A total of 15 sequences were generated and analyzed with 571 sequences previously published. The analises showed that the R119Q mutation seems to be related to HTLV-1 clinical conditions since the frequency of this HBZ mutation is significantly different in comparison between AC with HAM/TSP and ATLL. The R119Q mutation is possibly a protective factor as the frequency is higher in AC sequences.


Assuntos
Fatores de Transcrição de Zíper de Leucina Básica/genética , Variação Genética , Genoma Viral , Infecções por HTLV-I/virologia , Vírus Linfotrópico T Tipo 1 Humano/genética , Mutação , Proteínas dos Retroviridae/genética , Adulto , Genômica , Infecções por HTLV-I/sangue , Infecções por HTLV-I/classificação , Humanos , Leucócitos Mononucleares/virologia , Paraparesia Espástica Tropical/virologia , Carga Viral
11.
Nat Commun ; 12(1): 2296, 2021 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-33863880

RESUMO

Brazil experienced a large dengue virus (DENV) epidemic in 2019, highlighting a continuous struggle with effective control and public health preparedness. Using Oxford Nanopore sequencing, we led field and classroom initiatives for the monitoring of DENV in Brazil, generating 227 novel genome sequences of DENV1-2 from 85 municipalities (2015-2019). This equated to an over 50% increase in the number of DENV genomes from Brazil available in public databases. Using both phylogenetic and epidemiological models we retrospectively reconstructed the recent transmission history of DENV1-2. Phylogenetic analysis revealed complex patterns of transmission, with both lineage co-circulation and replacement. We identified two lineages within the DENV2 BR-4 clade, for which we estimated the effective reproduction number and pattern of seasonality. Overall, the surveillance outputs and training initiative described here serve as a proof-of-concept for the utility of real-time portable sequencing for research and local capacity building in the genomic surveillance of emerging viruses.


Assuntos
Vírus da Dengue/genética , Dengue/epidemiologia , Epidemias/prevenção & controle , Monitoramento Epidemiológico , Brasil/epidemiologia , Dengue/prevenção & controle , Dengue/transmissão , Dengue/virologia , Vírus da Dengue/isolamento & purificação , Estudos de Viabilidade , Variação Genética , Genoma Viral/genética , Humanos , Unidades Móveis de Saúde , Epidemiologia Molecular , Tipagem Molecular , Filogenia , Estudo de Prova de Conceito , RNA Viral/genética , RNA Viral/isolamento & purificação , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , Sequenciamento Completo do Genoma
13.
Infect Genet Evol ; 79: 104166, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31883457

RESUMO

The HTLV-1 is the first human retrovirus and is associated with several clinical syndromes, however, the pathogenesis of these clinical manifestations is still not fully understood. Furthermore, there are few complete genomes publicly available, about 0.12 complete genomes per 10,000 infected individuals and the databases have a major deficiency of sequences information. This study generated and characterized 31 HTLV-1 complete genomes sequences derived from individuals with Tropical Spastic Paraparesis/HTLV-1-Associated Myelopathy (TSP/HAM), Adult T-cell leukemia/lymphoma (ATL), infective dermatitis associated to HTLV-1 (IDH) and asymptomatic patients. These sequences are associated to clinical and epidemiological information about the patients. The sequencing data generated on Ion Torrent PGM platform were assembled and mapped against the reference HTLV-1 genome. These sequences were genotyped as Cosmopolitan subtype, Transcontinental subgroup. We identified the variants in the coding regions of the genome of the different clinical profiles, however, no statistical relation was detected. This study contributed to increase of HTLV-1 complete genomes in the world. Furthermore, to better investigate the contribution of HTLV-1 mutations for the disease outcome it is necessary to evaluate the interaction of the viral genome and characteristics of the human host.


Assuntos
Dermatite/virologia , Vírus Linfotrópico T Tipo 1 Humano/classificação , Leucemia-Linfoma de Células T do Adulto/virologia , Paraparesia Espástica Tropical/virologia , Sequenciamento Completo do Genoma/métodos , Adolescente , Adulto , Idoso , Criança , Feminino , Variação Genética , Tamanho do Genoma , Genoma Viral , Sequenciamento de Nucleotídeos em Larga Escala , Vírus Linfotrópico T Tipo 1 Humano/genética , Humanos , Masculino , Pessoa de Meia-Idade , Filogenia , Adulto Jovem
15.
AIDS Res Hum Retroviruses ; 35(9): 881-884, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31154802

RESUMO

The human T cell lymphotropic virus type 1 (HTLV-1) infects 5 to 10 million individuals and remains without specific treatment. This retrovirus genome is composed of the genes gag, pol, env, and a region known as pX. This region contains four open reading frames (ORFs) that encode specific proteins. The ORF-I produces the protein p12 and its cleavage product, p8. In this study, we analyzed the genetic diversity of 32 ORF-I sequences from patients with different clinical profiles. Seven amino acid changes with frequency over 5% were identified: G29S, P34L, L55F, F61L, S63P, F78L, and S91P. The identification of regions where the posttranslational sites were identified showed a high identity among the sequences and the amino acid changes exclusive of specific clinical profile were found in less than 5% of the samples. We compare the findings with 2.406 sequences available in GenBank. The low overall genetic diversity found suggested that this region could be used in the HTLV-1 vaccine development.


Assuntos
Variação Genética , Infecções por HTLV-I/virologia , Vírus Linfotrópico T Tipo 1 Humano/genética , Fases de Leitura Aberta , Proteínas Virais Reguladoras e Acessórias/genética , Infecções Assintomáticas , Bases de Dados de Ácidos Nucleicos , Endocardite/virologia , Humanos , Leucemia-Linfoma de Células T do Adulto/virologia , Mutação , Paraparesia Espástica Tropical/virologia
16.
Front Microbiol ; 10: 753, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31031729

RESUMO

Zika virus (ZIKV) is an arthropod-borne virus (arbovirus) in the Flavivirus genus of the Flaviviridae family. Since the large outbreaks in French Polynesia in 2013-2014 and in Brazil in 2015, ZIKV has been considered a new public health threat. Similar to other related flavivirus, ZIKV is associated with mild and self-limiting symptoms such as rash, pruritus, prostration, headache, arthralgia, myalgia, conjunctivitis, lower back pain and, when present, a short-term low grade fever. In addition, ZIKV has been implicated in neurological complications such as neonatal microcephaly and Guillain-Barré syndrome in adults. Herein, serum lipidomic analysis was used to identify possible alterations in lipid metabolism triggered by ZIKV infection. Patients who presented virus-like symptoms such as fever, arthralgia, headache, exanthema, myalgia and pruritus were selected as the control group. Our study reveals increased levels of several phosphatidylethanolamine (PE) lipid species in the serum of ZIKV patients, the majority of them plasmenyl-phosphatidylethanolamine (pPE) (or plasmalogens) linked to polyunsaturated fatty acids. Constituting up to 20% of total phospholipids in humans, plasmalogens linked to polyunsaturated fatty acids are particularly enriched in neural membranes of the brain. The biosynthesis of plasmalogens requires functional peroxisomes, which are important sites for viral replication, including ZIKV. Thus, increased levels of plasmalogens in serum of ZIKV infected subjects suggest a link between ZIKV life cycle and peroxisomes. Our data provide important insights into specific host cellular lipids that are likely associated with ZIKV replication and may serve as platform for antiviral strategy against ZIKV.

18.
Salvador; s.n; 2017. 76 p. ilus.
Tese em Português | LILACS | ID: biblio-1001000

RESUMO

INTRODUÇÃO: O HTLV-1 é o agente etiológico de doenças humanas, tais como leucemia/linfoma de célula T do adulto (ATLL), paraparesia espástica tropical/mielopatia associada ao HTLV (HAM/TSP), dermatite infectiva associada ao HTLV-1 (DIH), entre outras. Estima-se que cerca de 5-10 milhões de pessoas estejam infectadas pelo HTLV-1 no mundo e apesar dessa infecção ser endêmica em diferentes regiões geográficas, ainda permanece sem métodos terapêuticos eficazes. O genoma desse retrovírus é composto por duas fitas simples de RNA, com os genes gag, pol, env e uma região próxima à extremidade 3' conhecida como pX. A região pX contém quatro quadros abertos de leitura (ORFs) que codificam proteínas regulatórias específicas. A ORF-I codifica as proteínas p12 e p8, que quando expressas em quantidades equivalentes favorecem a infectividade e persistência viral. Mutações gênicas específicas na ORF-I do HTLV-1 podem alterar o padrão de expressão e, consequentemente, a concentração relativa destas proteínas, implicando na alteração da persistência viral e no desfecho da infecção. OBJETIVO: Caracterizar a ORF-I do HTLV-1 de pacientes com diferentes perfis clínicos. MATERIAL E MÉTODOS: Inicialmente foi realizada a anotação completa do principal genoma do HTLV-1 (ATK1), utilizado como sequência referência para a caracterização molecular da ORF-I. Em seguida, 1530 sequências da ORF-I provenientes de indivíduos assintomáticos e com HAM/TSP foram submetidas a análise de dataming para busca de associações entre mutações, carga proviral e sintomatologia. Para avaliar o grau de conservação genética da ORF-I em outros perfis clínicos, amostras de 23 pacientes assintomáticos, 11 pacientes com DIH, 13 com ATLL e 16...


INTRODUTION: The HTLV-1 is the etiological agent of some human diseases, such asadult T-cell leukaemia/lymphoma (ATLL), HTLV-1-associated myelopathy/tropicalspastic paraparesis (HAM/TSP), infective dermatitis associated to HTLV-1 (IDH),among others. It is estimated that approximately 5-10 million people are infected withHTLV-1 in the world and although this infection is endemic in different geographicregions, it still remains without effective therapeutic methods. The genome of thisretrovirus is composed of two single strands of RNA, with the genes gag, pol, env and aregion near the 3' end, known as pX. The pX region contains four open reading frames(ORFs) that encode specific regulatory proteins. The ORF-I encodes the p12 and p8proteins, which when expressed in equivalent concentrations favor infectivity and viralpersistence. Specific mutations in HTLV-1 ORF-I may alter the expression and,consequently, the relative concentration of these proteins, implying in viral persistence alteration and outcome of infection. OBJECTIVE: Characterize the HTLV-1 ORF-Ifrom patients with different clinical profiles. MATERIAL AND METHODS: First, thecomplete annotation of the main genome of HTLV-1 (ATK1), used as a referencesequence for the molecular characterization of ORF-I, was initially performed. Then,1530 ORF-I sequences from asymptomatic and HAM/TSP individuals were submitted todataming analysis to search associations. To assess the ORF-I genetic conservation statusin other clinical profiles, samples from 23 asymptomatic patients, 11 patients with IDH,13 with ATLL and 16 with...


Assuntos
Humanos , Mutação/fisiologia , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Vírus Linfotrópico T Tipo 1 Humano/patogenicidade
19.
Infect Genet Evol ; 45: 420-425, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27553711

RESUMO

The region known as pX in the 3' end of the human T-cell lymphotropic virus type 1 (HTLV-1) genome contains four overlapping open reading frames (ORF) that encode regulatory proteins. HTLV-1 ORF-I produces the protein p12 and its cleavage product p8. The functions of these proteins have been linked to immune evasion and viral infectivity and persistence. It is known that the HTLV-1 infection does not necessarily imply the development of pathological processes and here we evaluated whether natural mutations in HTLV-1 ORF-I can influence the proviral load and clinical manifestation of HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). For that, we performed molecular characterization, datamining and phylogenetic analysis with HTLV-1 ORF-I sequences from 156 patients with negative or positive diagnosis for HAM/TSP. Our analyses demonstrated that some mutations may be associated with the outcome of HAM/TSP (C39R, L40F, P45L, S69G and R88K) or with proviral load (P34L and F61L). We further examined the presence of mutations in motifs of HBZ and observed that P45L mutation is located within the HBZ nuclear localization signal and was found more frequently between patients with HAM/TSP and high proviral load. These results indicate that some natural mutations are located in functional domains of ORF-I and suggests a potential association between these mutations and the proviral loads and development of HAM/TSP. Therefore it is necessary to conduct functional studies aimed at evaluating the impact of these mutations on the virus persistence and immune evasion.


Assuntos
Vírus Linfotrópico T Tipo 1 Humano/genética , Fases de Leitura Aberta/genética , Paraparesia Espástica Tropical/epidemiologia , Paraparesia Espástica Tropical/virologia , Humanos , Epidemiologia Molecular , Mutação/genética , RNA Viral/análise , RNA Viral/genética , Carga Viral
20.
Mem. Inst. Oswaldo Cruz ; 109(4): 448-451, 03/07/2014. tab, graf
Artigo em Inglês | LILACS | ID: lil-716298

RESUMO

Human T-cell lymphotropic virus type 1 (HTLV-1) is mainly associated with two diseases: tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM) and adult T-cell leukaemia/lymphoma. This retrovirus infects five-10 million individuals throughout the world. Previously, we developed a database that annotates sequence data from GenBank and the present study aimed to describe the clinical, molecular and epidemiological scenarios of HTLV-1 infection through the stored sequences in this database. A total of 2,545 registered complete and partial sequences of HTLV-1 were collected and 1,967 (77.3%) of those sequences represented unique isolates. Among these isolates, 93% contained geographic origin information and only 39% were related to any clinical status. A total of 1,091 sequences contained information about the geographic origin and viral subtype and 93% of these sequences were identified as subtype “a”. Ethnicity data are very scarce. Regarding clinical status data, 29% of the sequences were generated from TSP/HAM and 67.8% from healthy carrier individuals. Although the data mining enabled some inferences about specific aspects of HTLV-1 infection to be made, due to the relative scarcity of data of available sequences, it was not possible to delineate a global scenario of HTLV-1 infection.


Assuntos
Adulto , Feminino , Humanos , Masculino , Infecções por HTLV-I/epidemiologia , Infecções por HTLV-I/virologia , Vírus Linfotrópico T Tipo 1 Humano/genética , Sequência de Bases , Mineração de Dados , Bases de Dados de Ácidos Nucleicos , Geografia Médica , Saúde Global , Epidemiologia Molecular , Interface Usuário-Computador
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