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1.
BMC Infect Dis ; 20(1): 470, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32615937

RESUMO

BACKGROUND: Strongyloidiasis is a gastrointestinal parasitic infection caused by percutaneous infection with Strongyloides stercoralis. Digestive symptoms such as diarrhea and abdominal pain are the main manifestation, but serious infections such as septicemia, purulent meningitis, and bacterial pneumonia may occur in individuals harboring human T-lymphotropic virus type 1 (HTLV-1) or who are immunocompromised. Although coinfection with Strongyloides stercoralis and HTLV-1 can lead to chronic strongyloidiasis and a disseminated form of the disease, there is a high rate of response to the anthelmintic ivermectin. CASE PRESENTATION: We report a case of strongyloidiasis infection syndrome that was difficult to differentiate from immune reconstitution inflammatory syndrome (IRIS) for various reasons. The patient had been treated with the corticosteroids tacrolimus (Tac) and mycophenolate mofetil (MMF) for systemic lupus erythematosus (SLE) with lupus nephritis and pancytopenia. When the steroid was reduced, she developed cytomegalovirus (CMV) enteritis, and her respiratory status rapidly deteriorated immediately after the withdrawal of Tac and MMF. It was difficult to distinguish immune reconstitution inflammatory syndrome from strongyloidiasis infection syndrome because stool cultures were negative and eosinophils were not increased. Bronchoscopy revealed viable Strongyloides, leading to a diagnosis of strongyloidiasis infection syndrome, but the patient died despite treatment. CONCLUSIONS: Both corticosteroid therapy and HTLV-1 infection can be associated with a decrease of eosinophils, despite the presence of parasitic infection. In conclusion, even if multiple culture tests are negative, the risk of parasitic infection should be assessed in patients receiving immunosuppressants and steroids even in non-endemic areas.


Assuntos
Infecções por Citomegalovirus/complicações , Citomegalovirus/imunologia , Infecções por HTLV-I/complicações , Vírus Linfotrópico T Tipo 1 Humano/isolamento & purificação , Imunossupressão/efeitos adversos , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Strongyloides stercoralis/isolamento & purificação , Estrongiloidíase/complicações , Idoso , Animais , Anti-Helmínticos/uso terapêutico , Antivirais/uso terapêutico , Coinfecção/tratamento farmacológico , Citomegalovirus/isolamento & purificação , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/virologia , Evolução Fatal , Feminino , Ganciclovir/uso terapêutico , Infecções por HTLV-I/diagnóstico , Infecções por HTLV-I/tratamento farmacológico , Infecções por HTLV-I/virologia , Humanos , Hospedeiro Imunocomprometido , Imunossupressores/efeitos adversos , Ivermectina/uso terapêutico , Estrongiloidíase/diagnóstico , Estrongiloidíase/tratamento farmacológico , Estrongiloidíase/parasitologia , Síndrome
2.
PLoS Negl Trop Dis ; 14(7): e0008361, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32667912

RESUMO

Human T-cell leukemia virus type 1 (HTLV-1) causes incurable adult T-cell leukemia and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Patients with HAM/TSP have increased levels of HTLV-1-infected cells compared with asymptomatic HTLV-1 carriers. However, the roles of cellular genes in HTLV-1-infected CD4+ T cells await discovery. We performed microarray analysis of CD4+ T cells from HAM/TSP patients and found that the ABL1 is an important gene in HAM/TSP. ABL1 is a known survival factor for T- and B-lymphocytes and is part of the fused gene (BCR-ABL) known to be responsible for chronic myelogenous leukemia (CML). ABL1 tyrosine kinase inhibitors (TKIs), including imatinib, nilotinib, and dasatinib, are used clinically for treating CML. To evaluate whether ABL1 is indeed important for HAM/TSP, we investigated the effect of TKIs on HTLV-1-infected cells. We developed a propidium monoazide-HTLV-1 viability quantitative PCR assay, which distinguishes DNA from live cells and dead cells. Using this method, we were able to measure the HTLV-1 proviral load (PVL) in live cells alone when peripheral blood mononuclear cells (PBMCs) from HAM/TSP cases were treated with TKIs. Treating the PBMCs with nilotinib or dasatinib induced significant reductions in PVL (21.0% and 17.5%, respectively) in live cells. Furthermore, ABL1 siRNA transfection reduced cell viability in HTLV-1-infected cell lines, but not in uninfected cell lines. A retrospective survey based on our clinical records found a rare case of HAM/TSP who also suffered from CML. The patient showed an 84.2% PVL reduction after CML treatment with imatinib. We conclude that inhibiting the ABL1 tyrosine kinase specifically reduced the PVL in PBMCs from patients with HAM/TSP, suggesting that ABL1 is an important gene for the survival of HTLV-1-infected cells and that TKIs may be potential therapeutic agents for HAM/TSP.


Assuntos
Infecções por HTLV-I/complicações , Vírus Linfotrópico T Tipo 1 Humano/fisiologia , Leucócitos Mononucleares/virologia , Paraparesia Espástica Tropical/enzimologia , Doenças da Medula Espinal/enzimologia , Adulto , Idoso , DNA Viral/genética , Feminino , Infecções por HTLV-I/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Paraparesia Espástica Tropical/tratamento farmacológico , Paraparesia Espástica Tropical/etiologia , Paraparesia Espástica Tropical/genética , Inibidores de Proteínas Quinases/administração & dosagem , Proteínas Proto-Oncogênicas c-abl/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-abl/genética , Proteínas Proto-Oncogênicas c-abl/metabolismo , Provírus/genética , Provírus/fisiologia , Estudos Retrospectivos , Doenças da Medula Espinal/tratamento farmacológico , Doenças da Medula Espinal/etiologia , Doenças da Medula Espinal/genética , Carga Viral
3.
PLoS One ; 15(5): e0232783, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32369533

RESUMO

INTRODUCTION: Human pegivirus 1 (HPgV-1) is a single-stranded, positive-sense RNA virus belonging to the Flaviviridae family with limited cause-effect evidence of the causation of human diseases. However, studies have shown a potential beneficial impact of HPgV-1 coinfection in HIV disease progression. Human T lymphotropic virus-1 (HTLV-1) is a retrovirus known for causing diseases, especially in muscle and white blood cells, in approximately 5% of patients. Thus, this study aimed to investigate the potential effects of an HPgV-1 infection in patients carrying HTLV-1 in the state of Pará in the North Region of Brazil. METHODS: A group of HTLV-1 carriers was compared to healthy controls. Blood samples were collected, data from medical regards were collected, and a questionnaire was administered. HPgV-1 and HTLV-1 positivity was determined by quantitative polymerase chain reaction (qRT-PCR). The data were analyzed to correlate the effects of HPgV-1 coinfection in HTLV-1 carriers. RESULTS: A total of 158 samples were included in the study: 74 HTLV-1-positive patients (46,8%) and 84 healthy controls (53,2%). The overall HPgV-1 positivity rate was 7.6% (12/158), resulting in a prevalence of 5.4% (4/74) and 9.5% (8/84) in HTLV-1 carriers and healthy controls, respectively. No significant differences were found when comparing any clinical or demographic data between groups. CONCLUSION: This study indicated that the prevalence of HPgV-1 infection is low in HTLV-1 carriers in Belém, Pará, and probably does not alter the clinical course of HTLV-1 infection, however, further studies are still needed.


Assuntos
Coinfecção/complicações , Infecções por Flaviviridae/complicações , Infecções por HTLV-I/complicações , Adulto , Brasil/epidemiologia , Coinfecção/epidemiologia , Feminino , Flaviviridae/isolamento & purificação , Infecções por Flaviviridae/epidemiologia , Infecções por HTLV-I/epidemiologia , Vírus Linfotrópico T Tipo 1 Humano/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência
4.
PLoS Negl Trop Dis ; 14(5): e0008245, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32453768

RESUMO

BACKGROUND: The WHO established targets for 2030 to globally reduce new viral hepatitis B and C infections by 90% and deaths by 65% and recommends searching for coinfections that increase the progression of chronic liver infections towards cirrhosis and hepatocellular carcinoma. AIMS AND METHODOLOGY: This study aimed to add information concerning the influence of human T-lymphotropic virus type 1 (HTLV-1) and type 2 (HTLV-2) infections in hepatitis B and C, since in Brazil, these human retroviruses are endemic but neglected. Serum samples from 1,910 patients with hepatitis B and 1,315 with hepatitis C from São Paulo, southeast Brazil, that were previously tested and grouped for HIV and HTLV-1/-2 coinfections were analyzed for hepatitis B virus (HBV) and hepatitis C virus (HCV) loads measurements and subsequent clearance using data from laboratory records. KEY RESULTS: Briefly, the lowest HBV viral load (VL) was detected in HBV/HTLV-2 coinfected patients, regardless of whether they were infected with HIV (all comparisons p<0.05). In contrast, higher HCV VL was detected in HCV/HIV, HCV/HIV/HTLV-1/-2 coinfected patients (all p<0.05), and the lowest HCV VL was detected in HCV/HTLV-2 coinfected patients. Curiously, 61.1% of the patients with HBV/HTLV-2 coinfection had an undetectable HBV VL at the beginning of the study versus 21.4% in the patients with HBV/HTLV-1 coinfection. Although the percentages of undetectable HCV loads in HCV/HTLV-1 and HCV/HTLV-2 coinfected patients were quite similar, during follow-up, more HCV clearance was detected in patients with HCV/HTLV-2 coinfection [OR 2.65; 95% IC (1.17-5.99)]. MAJOR CONCLUSIONS: HTLV-2 positively impacts HBV and HCV viral loads and HCV clearance, while HIV and/or HTLV-1 negatively impacts HCV viral load. Thus, the search for HTLV-1/-2 in viral hepatitis B and C infected patients has virological prognostic value, which is a strong reason to suggest including HTLV serology in the follow-up of patients.


Assuntos
Infecções por HTLV-I/complicações , Infecções por HTLV-II/complicações , Hepatite B/complicações , Hepatite C/complicações , Vírus Linfotrópico T Tipo 1 Humano , Vírus Linfotrópico T Tipo 2 Humano , Brasil/epidemiologia , Coinfecção , Infecções por HTLV-I/epidemiologia , Infecções por HTLV-II/epidemiologia , Hepatite B/epidemiologia , Hepatite C/epidemiologia , Humanos , Carga Viral
5.
PLoS Negl Trop Dis ; 14(4): e0008241, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32330142

RESUMO

BACKGROUND: Infective dermatitis associated with human T-cell lymphotropic virus type-1 (HTLV-1), (IDH), is a chronic eczema occurring in HTLV-1 infected children. Rare cases of adulthood IDH have been reported and no study until now aimed to compare juvenile and adulthood IDH. METHODOLOGY/PRINCIPAL FINDINGS: Twelve cases of adulthood IDH followed for a mean time of 7.5 years were analyzed according to clinicopathological and molecular aspects, comparing them to juvenile IDH cases. Diagnosis was based on the modified major criteria used for juvenile IDH. Proviral load (PVL) assessment was performed by real-time PCR technique. Adulthood IDH presented similar clinicopathological and molecular aspects compared to juvenile IDH. The morphology of lesions and areas of involvement were similar, except for the involvement of the ankles and inframammary folds in the adulthood form. HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) occurred in six adulthood IDH patients, with almost equal frequency. However, at least in two patients, HAM/TSP appeared prior to IDH, differently from what was observed in juvenile IDH. CONCLUSIONS/SIGNIFICANCE: Adulthood IDH is similar to juvenile IDH according to clinicopathological aspects and PVL levels. Therefore, the same modified major diagnostic criteria for juvenile IDH can be applied to both forms.


Assuntos
Eczema/patologia , Eczema/virologia , Infecções por HTLV-I/complicações , Vírus Linfotrópico T Tipo 1 Humano/isolamento & purificação , Provírus/isolamento & purificação , Carga Viral , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
7.
Intern Med ; 59(1): 129-133, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31434825

RESUMO

Recently, severe cases of infection due to hypermucoviscous Klebsiella pneumonia (hmKP) have been reported in Japan. The Amami Islands in Japan are also endemic regions for Strongyloides stercoralis. Disseminated strongyloidiasis strain often causes severe enterobacteria infection; however, whether or not chronic strongyloidiasis induces it remains unclear. We herein report a 71-year-old man who developed meningitis and liver abscess due to hmKP complicated with chronic strongyloidiasis. He died on the seventh hospital day. Strongyloides stercoralis were only found around the polyp in the cecum. Chronic strongyloidiasis can also induce severe infection due to enterobacteria, especially hypervirulent pathogens like hmKP, through the induction of mucosal rupture.


Assuntos
Infecções por HTLV-I/complicações , Infecções por Klebsiella/complicações , Abscesso Hepático/complicações , Meningoencefalite/complicações , Estrongiloidíase/complicações , Idoso , Alcoolismo/complicações , Doença Crônica , Evolução Fatal , Hepatite B Crônica/complicações , Vírus Linfotrópico T Tipo 1 Humano , Humanos , Japão , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae , Masculino , Estrongiloidíase/diagnóstico , Estrongiloidíase/tratamento farmacológico
8.
New Microbiol ; 43(1): 44-46, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31814031

RESUMO

Strongyloides stercoralis is a parasitic nematode with a worldwide distribution. It can go from an asymptomatic infection to a life-threatening hyperinfection syndrome. Here, we report a case of intestinal obstruction due to S. stercoralis in a pregnant woman. This condition, as well as severe strongyloidiasis in pregnant women, is seldomly reported. In this case, Human T-lymphotropic Virus 1 (HTLV-1) coinfection was confirmed, a well-known risk factor for a more severe presentation of strongyloidiasis. We suggest that HTLV status should be screened in every severe S. stercoralis infection, or when, despite a correct treatment, a relapse is observed.


Assuntos
Obstrução Intestinal , Complicações Parasitárias na Gravidez , Strongyloides stercoralis , Estrongiloidíase , Animais , Coinfecção , Feminino , Infecções por HTLV-I/complicações , Vírus Linfotrópico T Tipo 1 Humano/isolamento & purificação , Humanos , Obstrução Intestinal/etiologia , Gravidez , Complicações Parasitárias na Gravidez/parasitologia , Complicações Parasitárias na Gravidez/virologia , Strongyloides stercoralis/isolamento & purificação , Estrongiloidíase/complicações , Estrongiloidíase/parasitologia , Estrongiloidíase/virologia
9.
AIDS Rev ; 21(4): 211-217, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31834313

RESUMO

The human T-cell lymphotropic virus type 1 (HTLV-1) infects 5-10 million people worldwide and causes fatal and disabling diseases in a significant proportion of them. A chronic myelitis named HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) is the typical neurological manifestation of HTLV-1. However, other neurological syndromes can be either associated with HAM/TSP or occur in isolation in the HTLV-1 infected individual. Although this fact has been widely described over the years, it has been somewhat neglected by the mainstream literature, which has been largely focused on HAM/TSP. Cognitive dysfunction, encephalopathy, neurogenic bladder, motor neuron disease, inflammatory myopathies, polyneuropathy, and dysautonomia can also occur in the HTLV-1 infected patient and may remain unnoticed to the unsuspecting physician. In the present review, we intend to draw attention, primarily to the infectious disease specialist and to the general practitioner, to the fact that HTLV-1 has a broader neurological spectrum than the designation HAM/TSP suggests and that infected individuals may harbor other neurological syndromes in addition to HAM/TSP.


Assuntos
Infecções por HTLV-I/complicações , Doenças do Sistema Nervoso/epidemiologia , Doenças do Sistema Nervoso/patologia , Humanos
10.
Rev. esp. quimioter ; 32(6): 485-496, dic. 2019. ilus
Artigo em Inglês | IBECS | ID: ibc-190608

RESUMO

The Human T-Lymphotropic Virus type 1 (HTLV-1) affects up to 10 million people worldwide. It is directly associated to one of the most aggressive T cell malignancies: Adult T Cell Leukemia-Lymphoma (ATLL) and a progressive neurological disorder, Tropical Spastic Paraparesis/ HTLV-1 Associated Myelopathy (TSP/HAM). Also, infected patients tend to have more severe forms of infectious diseases such as Strongyloidiasis and Tuberculosis. HTLV spreads through parenteral, sexual, and vertical (mother-to-child) routes. Effective viral transmission is produced mainly by cell to cell mechanism, unlike other retroviruses such as HIV, which usually spread infecting cells in a cell-free form. HTLV also has a peculiar distribution, with clusters of high endemicity in nearby areas of very low prevalence or absence of the virus. This could be explained by factors including a possible founder effect, the predominance of mother to child transmission and the cell-to-cell trans-mission mechanisms. More data on viral epidemiology are needed in order to develop strategies in endemic areas aimed at reducing viral dissemination. In this review, we critically analyze HTLV-1 pathogenesis, epidemiology, diagnosis, associated diseases, preventive strategies, and treatments, with emphasis to the emerging risk for Europe and particularly Spain, focusing on prevention methods to avoid viral transmission and associated diseases


El Virus Linfotrópico Humano T tipo 1 (HTLV-1) afecta hasta a 10 millones de personas en todo el mundo. Está directamente asociado a una de las neoplasias malignas de células T más agresivas: Leucemia-Linfoma de células T del Adulto (LLTA) y a un trastorno neurológico progresivo: Paraparesia Espástica Tropical / Mielopatía Asociada a HTLV-1 (PET/MAH). Además, los pacientes infectados tienden a tener formas más graves de enfermedades infecciosas como la Estrongiloidiasis y Tuberculosis. El HTLV se propaga a través de las siguientes vías: parenteral, sexual y vertical. La transmisión viral efectiva se produce principalmente por el mecanismo de contacto directo de célula a célula, a diferencia de otros retrovirus como el VIH, que generalmente se propaga infectando a las células mediante partículas virales libres. El HTLV-1 tiene una distribución peculiar, con grupos de alta endemicidad en áreas cercanas de muy baja prevalencia o ausencia del virus. Esto podría explicarse por factores que incluyen un posible efecto fundador, el predominio de la transmisión vertical (leche materna) y los mecanismos de transmisión por contacto célula a célula. Hoy en día se necesitan más datos epidemiológicos para desarrollar estrategias en áreas endémicas, destinadas a reducir la diseminación viral. En esta revisión, se analiza la patogénesis, la epidemiología, el diagnóstico, las enfermedades asociadas, las estrategias preventivas y los tratamientos del HTLV-1, con énfasis en el riesgo emergente para Europa y particularmente España, centrándonos en los métodos de prevención para evitar la transmisión viral y las enfermedades asociadas


Assuntos
Humanos , Infecções por HTLV-I , Infecções por HTLV-I/complicações , Infecções por HTLV-I/diagnóstico , Infecções por HTLV-I/epidemiologia , Infecções por HTLV-I/etiologia , Medição de Risco
11.
Artigo em Inglês | MEDLINE | ID: mdl-31618373

RESUMO

Santa Catarina is a Brazilian State that has reported the lowest prevalence of human T-cell lymphotropic viruses (HTLV-1/2) in blood donors (0.04%). Although it presents ports, airports and roads that facilitate the entrance and dissemination of new infectious agents, no information exists concerning the HTLV-1/2 infections in HIV/AIDS patients. This study searched for HTLV-1/2 antibodies in plasma samples of 625 HIV/AIDS patients from the municipality of Tubarao (Southern Santa Catarina), and disclosed 1.1% of positivity (0.48% HTLV-1, 0.48% HTLV-2 and 0.16% untypeable HTLV), and a positive correlation with the male sex (OR 4.16) and intravenous drug use (OR 35.18). Although the percentage of 1.1% appears to be low, it is 27.5 times higher than the percentage detected in blood donors. Since HTLV-1 and HTLV-2 are circulating in HIV-infected individuals in Southern Santa Catarina, and these retroviruses could cause a differently impact on the HIV/AIDS outcomes, the surveillance of HTLV-1/2 is necessary, and it could support public health policies in preventing the transmission and dissemination of these viruses in this State.


Assuntos
Anticorpos Antivirais/sangue , Infecções por HIV/epidemiologia , Infecções por HTLV-I/epidemiologia , Infecções por HTLV-II/epidemiologia , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Vírus Linfotrópico T Tipo 2 Humano/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil/epidemiologia , Estudos Transversais , Monitoramento Epidemiológico , Feminino , Infecções por HIV/complicações , Infecções por HTLV-I/complicações , Infecções por HTLV-I/diagnóstico , Infecções por HTLV-II/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Adulto Jovem
12.
BMJ Case Rep ; 12(10)2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31645398

RESUMO

Human T-cell lymphotropic virus (HTLV) is a human oncoretrovirus known to cause adult T-cell leukaemia/lymphoma (ATLL). Coinfection of human T-lymphotropic virus type 1 with Epstein-Barr virus (EBV) results in enhanced expression of the HTLV virus and leads to aggressive organ involvement from T-cell malignancy. It has also been observed that the prevalence of hepatitis B infection has been higher in patients with HTLV ATLL as compared with the general population in certain countries. We describe a case of a 34-year-old man who initially presented with leucocytosis, fatigue and conjunctival erythema. His radiological images revealed significant generalised adenopathy, and his flow cytometry analysis came back positive for CD4-positive T-cell lymphoma. He was subsequently diagnosed with HTLV-positive ATLL. Ultimately the patient was also diagnosed with acute hepatitis B and EBV. We describe a unique case of ATLL with coinfection with two other viruses, the association of which can be of potential prognostic value in guiding the treatment strategies for ATLL.


Assuntos
Infecções por Vírus Epstein-Barr/complicações , Infecções por HTLV-I/complicações , Hepatite B/complicações , Leucemia-Linfoma de Células T do Adulto/virologia , Adulto , Coinfecção/virologia , Vírus da Hepatite B/isolamento & purificação , Herpesvirus Humano 4/isolamento & purificação , Vírus Linfotrópico T Tipo 1 Humano/isolamento & purificação , Humanos , Leucemia-Linfoma de Células T do Adulto/etiologia , Leucemia-Linfoma de Células T do Adulto/patologia , Masculino
13.
Retrovirology ; 16(1): 25, 2019 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-31492165

RESUMO

Of the members of the primate T cell lymphotropic virus (PTLV) family, only the human T-cell leukemia virus type-1 (HTLV-1) causes disease in humans-as the etiological agent of adult T-cell leukemia/lymphoma (ATLL), HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), and other auto-inflammatory disorders. Despite having significant genomic organizational and structural similarities, the closely related human T-cell lymphotropic virus type-2 (HTLV-2) is considered apathogenic and has been linked with benign lymphoproliferation and mild neurological symptoms in certain infected patients. The silencing of proviral gene expression and maintenance of latency are central for the establishment of persistent infections in vivo. The conserved pX sequences of HTLV-1 and HTLV-2 encode several ancillary factors which have been shown to negatively regulate proviral gene expression, while simultaneously activating host cellular proliferative and pro-survival pathways. In particular, the ORF-II proteins, HTLV-1 p30II and HTLV-2 p28II, suppress Tax-dependent transactivation from the viral promoter-whereas p30II also inhibits PU.1-mediated inflammatory-signaling, differentially augments the expression of p53-regulated metabolic/pro-survival genes, and induces lymphoproliferation which could promote mitotic proviral replication. The ubiquitinated form of the HTLV-1 p13II protein localizes to nuclear speckles and interferes with recruitment of the p300 coactivator by the viral transactivator Tax. Further, the antisense-encoded HTLV-1 HBZ and HTLV-2 APH-2 proteins and mRNAs negatively regulate Tax-dependent proviral gene expression and activate inflammatory signaling associated with enhanced T-cell lymphoproliferation. This review will summarize our current understanding of the pX latency-maintenance factors of HTLV-1 and HTLV-2 and discuss how these products may contribute to the differences in pathogenicity between the human PTLVs.


Assuntos
Vírus Linfotrópico T Tipo 1 Humano/genética , Vírus Linfotrópico T Tipo 2 Humano/genética , Fatores de Transcrição/genética , Proteínas Virais Reguladoras e Acessórias/genética , Latência Viral , Regulação Viral da Expressão Gênica , Infecções por HTLV-I/complicações , Infecções por HTLV-II/virologia , Vírus Linfotrópico T Tipo 1 Humano/patogenicidade , Vírus Linfotrópico T Tipo 2 Humano/patogenicidade , Humanos , Vírus Linfotrópico T Tipo 1 de Primatas/genética , Vírus Linfotrópico T Tipo 1 de Primatas/patogenicidade , Proteínas Oncogênicas de Retroviridae/genética , Proteínas Oncogênicas de Retroviridae/metabolismo
15.
Am J Trop Med Hyg ; 101(4): 848-850, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31436152

RESUMO

Strongyloides stercoralis and human T-lymphotropic virus 1 (HTLV-1) coinfections have been extensively reported in the literature, but the diagnosis and treatment of strongyloidiasis remains a challenge, particularly in HTLV-1 carriers. Our objectives were to evaluate the efficacy of a new PCR method for the detection of S. stercoralis in HTLV-1-positive patients. Stools were collected over a 1-year period across the endemic region of French Guiana, including remote forest areas. Two systems of real-time PCR were then used comparatively, with small subunit and specific repeat as respective targets, and compared with the results of microscopic examinations. One-hundred and twelve stool samples were included. Twenty-seven patients (24.1%) presented a positive HTLV-1 serology. The overall prevalence of strongyloidiasis among the 112 patients was 30% with small-subunit PCR and 11.6% with microscopic examinations. In the seropositive population, all tested stools were negative, whereas 51.2% were positive using small-subunit PCR. Thus, PCR allowed a much-improved sensitivity, particularly in HTLV-1 carriers. Among the two systems investigated, small subunit yielded better results than specific repeat PCR, with prevalence rates in HTLV-1 carriers of 51.2% and 22.2%, respectively. Therefore, PCR should be considered as a useful tool for the diagnosis of strongyloidiasis, particularly in HTLV-1 carriers who often present a light parasitic load due to erratic administration of anthelmintic drugs.


Assuntos
Coinfecção , Infecções por HTLV-I/complicações , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Reação em Cadeia da Polimerase em Tempo Real/métodos , Strongyloides stercoralis/isolamento & purificação , Estrongiloidíase/diagnóstico , Animais , Anti-Helmínticos/uso terapêutico , Sondas de DNA/genética , Fezes/parasitologia , Guiana Francesa/epidemiologia , Infecções por HTLV-I/epidemiologia , Infecções por HTLV-I/virologia , Humanos , Prevalência , Sensibilidade e Especificidade , Strongyloides stercoralis/genética , Estrongiloidíase/complicações , Estrongiloidíase/epidemiologia , Estrongiloidíase/parasitologia
16.
Rev Soc Bras Med Trop ; 52: e20180244, 2019 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-31340354

RESUMO

INTRODUCTION: Apart from masking the diagnosis of AIDS in patients with HIV/AIDS, human T-cell lymphotropic virus (HTLV), when present, also increases the risk of myelopathies and neurological disease in these patients. METHODS: Disease prevalence was estimated by ELISA and confirmed by Western blot. RESULTS: The coinfection rate was 1.5% (11/720); 10 of 11 patients had HTLV-1, and the remaining one had HTLV-2. The majority were male, over 40 years old, and of pardo color (ethnicity). CONCLUSIONS: There was no association between the risk factors examined and HTLV/HIV coinfection. This is the first study to report the occurrence of HTLV-2 in Pernambuco.


Assuntos
Coinfecção , Infecções por HIV/complicações , Infecções por HTLV-I/complicações , Infecções por HTLV-II/complicações , Adolescente , Adulto , Western Blotting , Brasil/epidemiologia , Ensaio de Imunoadsorção Enzimática , Feminino , Infecções por HIV/epidemiologia , Infecções por HTLV-I/epidemiologia , Infecções por HTLV-II/epidemiologia , Vírus Linfotrópico T Tipo 1 Humano , Vírus Linfotrópico T Tipo 2 Humano , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Fatores Socioeconômicos , Adulto Jovem
17.
Biochim Biophys Acta Mol Basis Dis ; 1865(10): 2633-2646, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31295529

RESUMO

N-myc downstream-regulated gene 2 (NDRG2) is a candidate tumor suppressor that is frequently downregulated in adult T-cell leukemia/lymphoma (ATLL) and functions to negatively regulate several cellular signaling pathways as PP2A recruiter. To clarify the molecular mechanisms of suppression of NDRG2 expression, we initially determined the expression pattern of NDRG2 in various types of T-cells and ATLL cells. NDRG2 expression was significantly upregulated in HTLV-1/Tax-immortalized T-cells, which was mediated by NF-κB activation through Tax expression. On the other hand, NDRG2 expression was suppressed in HTLV-1-infected cell lines and various types of ATLL cells, which was dependent on the DNA methylation of the NDRG2 promoter. We found that the expression of enhancer of zeste homolog 2 (EZH2), a member of the polycomb family, is increased in ATLL, and that EZH2 directly binds to the NDRG2 promoter and induces DNA methylation of the NDRG2 promoter. Since the expression of EZH2 were anti-parallelly regulated with the NDRG2 expression, EZH2 might be one of the most important regulators of the downregulation of NDRG2, contributing to enhanced activation of signaling pathways during ATLL development.


Assuntos
Infecções por HTLV-I/complicações , Leucemia-Linfoma de Células T do Adulto/genética , Leucemia-Linfoma de Células T do Adulto/metabolismo , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Adulto , Linhagem Celular Tumoral , Proliferação de Células , Metilação de DNA , Regulação para Baixo , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Regulação Neoplásica da Expressão Gênica , Vírus Linfotrópico T Tipo 1 Humano , Humanos , NF-kappa B/metabolismo , Transdução de Sinais , Linfócitos T , Regulação para Cima
18.
Asian Pac J Cancer Prev ; 20(6): 1909-1912, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-31244317

RESUMO

Background: Human T-cell lymphotropic virus type 1 (HTLV-1) is a retrovirus that causes adult T-cell leukemia/lymphoma (ATL), an aggressive form of T-cell malignancy. The relationship between HTLV-1 infection and cancer progression is controversial. HTLV-1 encodes oncogenic protein TAX1 and it is hypothesized that HTLV-1 infection is associated with breast cancer progression. In this study, we evaluated the relationship between HTLV-1 infection and clinicopathological factors in breast cancer patients. Methods: We retrospectively analyzed 610 patients with primary breast cancer who underwent surgical treatment without preoperative chemotherapy at Kagoshima University Hospital between January 2001 and January 2015. Results: When patients with and without HTLV-1 infection were compared, no differences in clinicopathological factors were observed, except for age. Disease-free survival and overall survival rates did not differ between groups. Conclusions: HTLV-1­positive patients were significantly older than HTLV-1­negative patients. It was supposed to be due to the fact that the HTLV-1 infection rate is decreasing. Any effect of HTLV-1 infection on breast cancer progression appears to be negligibly small.


Assuntos
Neoplasias da Mama/patologia , Infecções por HTLV-I/complicações , Vírus Linfotrópico T Tipo 1 Humano/patogenicidade , Recidiva Local de Neoplasia/patologia , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/virologia , Feminino , Seguimentos , Infecções por HTLV-I/virologia , Humanos , Incidência , Japão/epidemiologia , Metástase Linfática , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/virologia , Prognóstico , Estudos Retrospectivos
19.
Microb Pathog ; 134: 103578, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31175973

RESUMO

Atherosclerosis is a multifactorial life-threatening disease which an epidemiologic study in Northeastern Iran showed its association with HTLV-1 infection. Therefore, a cross-sectional study of 39 newly diagnosed subjects with angiography test in three groups including 14 coronary artery disease+HTLV-1+ (CAD+HTLV-1+), 8 CAD-HTLV-1+, and 17 CAD+HTLV-1- patients and 11 healthy subjects (CAD-HTLV-1-) were conducted. In the present study, Tax and proviral load (PVL) as HTLV-1 virulence factors, along with host chemokine receptor 1 (CCR1), and CCR2 were investigated. Real-time PCR TaqMan method was carried out for PVL measurement and HTLV-1-Tax, CCR1, and CCR2 expressions in peripheral blood mononuclear cells (PBMCs). Furthermore, the main risk factors, lipid profile, and complete blood count (CBC) were assessed. Expression of CCR1 in CAD+HTLV-1+ group was higher than CAD-HTLV-1+ (P = 0.01) and healthy subjects (P = 0.02). Expression of CCR1 in CAD+HTLV-1+ was higher in comparison with CAD+HTLV-1-group but did not meet 95% CI (P = 0.02), but meaningful at 91% CI. In addition, expression of CCR2 in CAD+HTLV-1+ subjects was higher than CAD-HTLV-1+ and CAD+HTLV-1- (P = 0.001, P = 0.005, respectively). In CAD+HTLV-1- subjects, CCR2 was higher than CAD-HTLV-1+ (P = 0.03). The mean PVL in CAD+HTLV-1+ group is more than CAD-HTLV-1+ (P = 0.041). In HTLV-1+ patients Tax had a positive correlation with cholesterol (R = 0.59, P = 0.01), LDL (R = 0.79, P = 0.004) and a negative correlation with HDL (R = -0.47, P = 0.04). These correlations were stronger in CAD+HTLV-1+. Findings showed that HTLV-1 could alter the expression of CCR2 and, less effect, on CCR1. Moreover, the strong correlation between CCR2 and HTLV-1-Tax with cholesterol, LDL and HDL showed that Tax as the main HTLV-1 virulence factor in cytokine deregulation might be had indirect effects on cholesterol, LDL, and HDL levels.


Assuntos
Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/virologia , Infecções por HTLV-I/complicações , Infecções por HTLV-I/virologia , Vírus Linfotrópico T Tipo 1 Humano/patogenicidade , Idoso , Aterosclerose/epidemiologia , Aterosclerose/virologia , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Doença da Artéria Coronariana/etiologia , Doença da Artéria Coronariana/virologia , Estudos Transversais , Citocinas/sangue , Feminino , Infecções por HTLV-I/epidemiologia , Humanos , Irã (Geográfico) , Leucócitos Mononucleares/virologia , Masculino , Pessoa de Meia-Idade , Provírus , Reação em Cadeia da Polimerase em Tempo Real , Receptores CCR1/sangue , Receptores CCR1/metabolismo , Receptores CCR2/sangue , Receptores CCR2/metabolismo , Fatores de Risco , Carga Viral , Fatores de Virulência
20.
Rev Soc Bras Med Trop ; 52: e20180481, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31166487

RESUMO

INTRODUCTION: Human T-cell lymphotropic virus type 1 (HTLV-1)-associated inflammatory diseases are not well understood; however, their clinical manifestations may be influenced by the host genetic background. METHODS: We genotyped 298 individuals with HTLV-1 and 380 controls for interleukin-10 (IL10) gene variants-rs3024496, rs1800871, rs1800896-and used logistic regression analysis to determine their association with clinical phenotypes. RESULTS: No association with HTLV-1 infection was observed. However, allele A of rs1800896 (1082bp upstream) was associated with protection against neurological impairment, specifically overactive bladder (OR=0.447, 95% CI 0.28-0.70, p=0.001). CONCLUSIONS: Our data suggests that IL10 regulation ameliorates neurological damage in HTLV-1 infections.


Assuntos
Infecções por HTLV-I/genética , Interleucina-10/genética , Polimorfismo de Nucleotídeo Único/genética , Bexiga Urinária Hiperativa/genética , Adolescente , Adulto , Estudos de Casos e Controles , Feminino , Genótipo , Infecções por HTLV-I/complicações , Vírus Linfotrópico T Tipo 1 Humano , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Bexiga Urinária Hiperativa/etiologia , Adulto Jovem
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