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Retrovirology Aug 2019Human T cell leukemia virus type 1 (HTLV-1) was the first discovered human retrovirus and the etiologic agent of adult T-cell leukemia and HTLV-1-associated... (Comparative Study)
Comparative Study Review
Human T cell leukemia virus type 1 (HTLV-1) was the first discovered human retrovirus and the etiologic agent of adult T-cell leukemia and HTLV-1-associated myelopathy/tropical spastic paraparesis. Shortly after the discovery of HTLV-1, human T-cell leukemia virus type 2 (HTLV-2) was isolated from a patient with hairy cell leukemia. Despite possession of similar structural features to HTLV-1, HTLV-2 has not been definitively associated with lymphoproliferative disease. Since their discovery, studies have been performed with the goal of highlighting the differences between HTLV-1 and HTLV-2. A better understanding of these differences will shed light on the specific pathogenic mechanisms of HTLV-1 and lead to novel therapeutic targets. This review will compare and contrast the two oldest human retroviruses with regards to epidemiology, genomic structure, gene products, and pathobiology.
Topics: HTLV-I Infections; HTLV-II Infections; Human T-lymphotropic virus 1; Human T-lymphotropic virus 2; Humans; Leukemia-Lymphoma, Adult T-Cell; Leukocytes, Mononuclear; Paraparesis, Tropical Spastic
PubMed: 31391116
DOI: 10.1186/s12977-019-0483-0 -
PLoS Neglected Tropical Diseases Jan 2017HTLV-1 is the causative agent of a severe form of adult T cell leukemia/Lymphoma (ATL), and of a chronic progressive neuromyelopathy designated HTLV-1 associated...
HTLV-1 is the causative agent of a severe form of adult T cell leukemia/Lymphoma (ATL), and of a chronic progressive neuromyelopathy designated HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). Two important HTLV-1-encoded proteins, Tax-1 and HBZ, play crucial roles in the generation and maintenance of the oncogenic process. Less information is instead available on the molecular and cellular mechanisms leading to HAM/TSP. More importantly, no single specific biomarker has been described that unambiguously define the status of HAM/TSP. Here we report for the first time the finding that HBZ, described until now as an exclusive nuclear protein both in chronically infected and in ATL cells, is instead exclusively localized in the cytoplasm of peripheral blood mononuclear cells (PBMC) from patients suffering of HAM/TSP. Interestingly, at the single cell level, HBZ and Tax-1 proteins are never found co-expressed in the same cell, suggesting the existence of mechanisms of expression uncoupling of these two important HTLV-1 viral products in HAM/TSP patients. Cells expressing cytoplasmic HBZ were almost exclusively found in the CD4+ T cell compartment that was not, at least in a representative HAM/TSP patient, expressing the CD25 marker. Less than 1 percent CD8+ T cells were fond positive for HBZ, while B cells and NK cells were found negative for HBZ in HAM/TSP patients. Our results identify the cytoplasmic localization of HBZ in HAM/TSP patient as a possible biomarker of this rather neglected tropical disease, and raise important hypotheses on the role of HBZ in the pathogenesis of the neuromyelopathy associated to HTLV-1 infection.
Topics: Basic-Leucine Zipper Transcription Factors; Biomarkers; CD4-Positive T-Lymphocytes; Cytoplasm; HTLV-I Infections; Human T-lymphotropic virus 1; Humans; Leukemia-Lymphoma, Adult T-Cell; Leukocytes, Mononuclear; Paraparesis, Tropical Spastic; Protein Transport; Retroviridae Proteins; Spinal Cord Diseases
PubMed: 28095504
DOI: 10.1371/journal.pntd.0005285 -
Antiviral Research Jan 2017Even though an estimated 10-20 million people worldwide are infected with the oncogenic retrovirus, human T-lymphotropic virus type 1 (HTLV-1), its epidemiology is... (Review)
Review
Even though an estimated 10-20 million people worldwide are infected with the oncogenic retrovirus, human T-lymphotropic virus type 1 (HTLV-1), its epidemiology is poorly understood, and little effort has been made to reduce its prevalence. In response to this situation, the Global Virus Network launched a taskforce in 2014 to develop new methods of prevention and treatment of HTLV-1 infection and promote basic research. HTLV-1 is the etiological agent of two life-threatening diseases, adult T-cell leukemia and HTLV-associated myelopathy/tropical spastic paraparesis, for which no effective therapy is currently available. Although the modes of transmission of HTLV-1 resemble those of the more familiar HIV-1, routine diagnostic methods are generally unavailable to support the prevention of new infections. In the present article, the Taskforce proposes a series of actions to expand epidemiological studies; increase research on mechanisms of HTLV-1 persistence, replication and pathogenesis; discover effective treatments; and develop prophylactic and therapeutic vaccines.
Topics: Advisory Committees; Biomedical Research; Cost of Illness; Global Health; HIV Infections; HTLV-I Infections; Human T-lymphotropic virus 1; Humans; Leukemia-Lymphoma, Adult T-Cell; Paraparesis, Tropical Spastic; Spinal Cord Diseases
PubMed: 27840202
DOI: 10.1016/j.antiviral.2016.10.015 -
Cadernos de Saude Publica 2019HTLV is a virus that affects human T-cells. Brazil is the country of the world with the largest absolute number of HTLV cases. Estimates by the Ministry of Health point... (Review)
Review
HTLV is a virus that affects human T-cells. Brazil is the country of the world with the largest absolute number of HTLV cases. Estimates by the Ministry of Health point to 700,000 to 2 million infected Brazilians. The majority are asymptomatic carriers, but some persons may develop degenerative neurological conditions such as tropical spastic paraparesis, in addition to leukemia and lymphoma. The forms of transmission and clinical manifestations such as progressive motor incapacity, genitourinary disorders, in addition to restriction of maternal breastfeeding, impact daily life and can lead to social discrimination and stigma. The stigma denotes violation of social norms and reinforces prejudice and inequalities. This article aims to discuss the concept of stigma and its repercussions on persons living with HTLV. The discussion is based on a literature review on the theme and the authors' experience with care for persons affected by the infection and illness. The study found that both HTLV carrier status and HTLV-related illness can be stigmatizing for individuals, who feel inferior for being infected with a potentially serious and even fatal disease, although incompletely understood and loaded with derogatory stereotypes. This situation can have negative repercussions on access to health services, treatment adherence, and pursuit of rights. Public policies should help mitigate such stigmatization, ensuring the rights of individuals in a situation of vulnerability due to HTLV in order from them to live as protagonists in the exercise of their civil rights.
Topics: Deltaretrovirus Infections; HIV Infections; Humans; Paraparesis, Tropical Spastic; Prejudice; Social Discrimination; Social Stigma; Stereotyping
PubMed: 31721899
DOI: 10.1590/0102-311X00005419 -
Journal of Ayub Medical College,... 2019Thyrotoxic periodic paralysis is an uncommon disorder characterized by hypokalaemia, thyrotoxicosis and paralysis, most commonly seen in South Asian males. Aim of our...
Thyrotoxic periodic paralysis is an uncommon disorder characterized by hypokalaemia, thyrotoxicosis and paralysis, most commonly seen in South Asian males. Aim of our case series is to highlight the significance of this reversible cause of patients presenting with neuromuscular paralysis. We present case series of 1 Asian and three Caucasian patients with thyrotoxic periodic paralysis who came with neuromuscular weakness secondary to thyrotoxicosis. All made a swift and uneventful recovery with no recurrence. Thyrotoxic periodic paralysis (TPP) is an infrequent condition having recurrent episodes of muscle weakness as main feature. Hypokalaemia is a common finding seen in these patients. Resolution of the attacks is achieved with correction of hypokalaemia and hyperthyroidism.
Topics: Adult; Aged, 80 and over; Female; Humans; Hyperthyroidism; Hypokalemia; Male; Muscle Weakness; Paralysis; Thyrotoxicosis; Young Adult
PubMed: 31933322
DOI: No ID Found -
Frontiers in Immunology 2022Human T cell leukemia virus-1 (HTLV-1) is the causative agent of a severe cancer of the lymphoid lineage that develops in 3-5% of infected individuals after many years.... (Review)
Review
Human T cell leukemia virus-1 (HTLV-1) is the causative agent of a severe cancer of the lymphoid lineage that develops in 3-5% of infected individuals after many years. HTLV-1 infection may also induce a serious inflammatory pathology of the nervous system designated HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Two virus-encoded proteins, the viral transactivator Tax-1 and the HTLV-1 basic leucine-zipper factor HBZ, are strongly involved in the oncogenic process. Tax-1 is involved in initial phases of the oncogenic process. Conversely, HBZ seems to be involved in maintenance of the neoplastic state as witnessed by the generation of leukemic/lymphomatous phenotype in HBZ transgenic mice and the persistent expression of HBZ in all phases of the oncogenic process. Nevertheless, the intimate molecular and cellular mechanism mediated by the two viral proteins, particularly HBZ, in oncogenesis still remain elusive. An important step toward the complete comprehension of HBZ-associated oncogenicity is the clarification of the anatomical correlates of HBZ during the various phases of HTLV-1 infection to development of HTLV-1-associated inflammatory pathology and ultimately to the establishment of leukemia. In this review, I will summarize recent studies that have established for the first time a temporal and unidirectional expression of HBZ, beginning with an exclusive cytoplasmic localization in infected asymptomatic individuals and in HAM/TSP patients and ending to a progressive cytoplasmic-to-nuclear transition in leukemic cells. These results are framed within the present knowledge of HTLV-1 infection and the future lines of research that may shed new light on the complex mechanism of HTLV-1- mediated oncogenesis.
Topics: Animals; Basic-Leucine Zipper Transcription Factors; Carcinogenesis; Human T-lymphotropic virus 1; Leukemia; Mice; Paraparesis, Tropical Spastic; Retroviridae Proteins; Viral Proteins
PubMed: 35812456
DOI: 10.3389/fimmu.2022.940131 -
Children (Basel, Switzerland) Jun 2021Extensive limb lengthening (ELL) was completed in 75 patients: 66 achondroplasia and 9 hypochondroplasia. The average lengthening was 27 cm for achondroplasia (12-40 cm)... (Review)
Review
Extensive limb lengthening (ELL) was completed in 75 patients: 66 achondroplasia and 9 hypochondroplasia. The average lengthening was 27 cm for achondroplasia (12-40 cm) and 17 cm for hypochondroplasia (range 10-25 cm). There were 48 females and 27 males. Lengthening was done either by 2-segment (14 patients; both tibias and/or both femurs) or by 4-segment lengthenings (64 patients; both femurs and tibias at the same time). Most patients also had bilateral humeral lengthening. Patients had 2 or 3 lower limb lengthenings and one humeral lengthening. Lengthenings were either juvenile-onset (31), adolescent-onset (38) or adult-onset (6). The average age at final follow-up was 26 years old (range 17-43 years). There were few permanent sequelae of complications. The most serious was one paraparesis. All patients returned to activities of normal living and only one was made worse by the surgery (paraparesis). This is the first study to show that ELL can lead to an increase of height into the normal height range. Previous studies showed mean increases of height of up to 20 cm, while this study consistently showed an average increase of 30 cm (range 15-40 cm) for juvenile-onset and mean increase of 26 cm (range 15-30 cm) for adolescent-onset. This results in low normal height at skeletal maturity for males and females. The adult-onset had a mean increase of 16.8 (range 12-22 cm). This long-term follow-up study shows that ELL can be done safely even with large lengthenings and that 4-segment lengthening may offer advantages over 2-segment lengthening. While all but the more recent cases were performed using external fixation, implantable limb lengthening promises to be an excellent alternative and perhaps an improvement.
PubMed: 34202538
DOI: 10.3390/children8070540 -
Frontiers in Immunology 2022Human T-cell leukemia virus-1 (HTLV-1) is a retrovirus that persistently infects CD4+ T-cells, and is the causative agent of adult T-cell leukemia/lymphoma (ATLL),... (Review)
Review
Human T-cell leukemia virus-1 (HTLV-1) is a retrovirus that persistently infects CD4+ T-cells, and is the causative agent of adult T-cell leukemia/lymphoma (ATLL), tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM) and several inflammatory diseases. T-cell transformation by HTLV-1 is driven by multiple interactions between viral regulatory proteins and host cell pathways that govern cell proliferation and survival. Studies performed over the last decade have revealed alterations in the expression of many microRNAs in HTLV-1-infected cells and ATLL cells, and have identified several microRNA targets with roles in the viral life cycle and host cell turnover. This review centers on miR-150-5p, a microRNA whose expression is temporally regulated during lymphocyte development and altered in several hematological malignancies. The levels of miR-150-5p are reduced in many HTLV-1-transformed- and ATLL-derived cell lines. Experiments in these cell lines showed that downregulation of miR-150-5p results in activation of the transcription factor STAT1, which is a direct target of the miRNA. However, data on miR-150-5p levels in freshly isolated ATLL samples are suggestive of its upregulation compared to controls. These apparently puzzling findings highlight the need for more in-depth studies of the role of miR-150-5p in HTLV-1 infection and pathogenesis based on knowledge of miR-150-5p-target mRNA interactions and mechanisms regulating its function in normal leukocytes and hematologic neoplasms.
Topics: CD4-Positive T-Lymphocytes; Human T-lymphotropic virus 1; Humans; Leukemia-Lymphoma, Adult T-Cell; MicroRNAs; Paraparesis, Tropical Spastic
PubMed: 36072598
DOI: 10.3389/fimmu.2022.974088 -
Frontiers in Immunology 2022Human T lymphotropic virus 1 (HTLV-1) is a human retrovirus identified as the causative agent in adult T-cell leukemia/lymphoma (ATL) and chronic-progressive... (Review)
Review
Human T lymphotropic virus 1 (HTLV-1) is a human retrovirus identified as the causative agent in adult T-cell leukemia/lymphoma (ATL) and chronic-progressive neuroinflammatory disorder HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-1 is estimated to infect between 5-20 million people worldwide, although most infected individuals remain asymptomatic. HTLV-1 infected persons carry an estimated lifetime risk of approximately 5% of developing ATL, and between 0.25% and 1.8% of developing HAM/TSP. Most HTLV-1 infection is detected in CD4 T cells which causes the aggressive malignancy in ATL. In HAM/TSP, the increase of HTLV-1 provirus induces immune dysregulation to alter inflammatory milieu, such as expansion of HTLV-1-specific CD8 T cells, in the central nervous system of the infected subjects, which have been suggested to underlie the pathogenesis of HAM/TSP. Factors contributing to the conversion from asymptomatic carrier to disease state remain poorly understood. As such, the identification and tracking of HTLV-1-specific T cell biomarkers that may be used to monitor the progression from primary infection to immune dysfunction and disease are of great interest. T cell receptor (TCR) repertoires have been extensively investigated as a mechanism of monitoring adaptive T cell immune response to viruses and tumors. Breakthrough technologies such as single-cell RNA sequencing have increased the specificity with which T cell clones may be characterized and continue to improve our understanding of TCR signatures in viral infection, cancer, and associated treatments. In HTLV-1-associated disease, sequencing of TCR repertoires has been used to reveal repertoire patterns, diversity, and clonal expansions of HTLV-1-specific T cells capable of immune evasion and dysregulation in ATL as well as in HAM/TSP. Conserved sequence analysis has further been used to identify CDR3 motif sequences and exploit disease- or patient-specificity and commonality in HTLV-1-associated disease. In this article we review current research on TCR repertoires and HTLV-1-specific clonotypes in HTLV-1-associated diseases ATL and HAM/TSP and discuss the implications of TCR clonal expansions on HTLV-1-associated disease course and treatments.
Topics: Adult; Biomarkers; CD8-Positive T-Lymphocytes; Human T-lymphotropic virus 1; Humans; Paraparesis, Tropical Spastic; Receptors, Antigen, T-Cell
PubMed: 36189294
DOI: 10.3389/fimmu.2022.984274