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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 -
Revista Espanola de Quimioterapia :... Dec 2019The 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:... (Review)
Review
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.
Topics: HTLV-I Infections; Humans; Risk Assessment
PubMed: 31648512
DOI: No ID Found -
Annals of Clinical and Translational... Apr 2022In the diagnosis of HTLV-1-associated myelopathy (HAM), while magnetic resonance imaging (MRI) is essential to exclude other diseases, its power is limited regarding HAM...
OBJECTIVE
In the diagnosis of HTLV-1-associated myelopathy (HAM), while magnetic resonance imaging (MRI) is essential to exclude other diseases, its power is limited regarding HAM diagnosis, as only 30% of affected patients present with spinal cord atrophy. Diffusion tensor imaging (DTI) may enable the detection of damage in the white matter microstructure. Here, we quantitatively assess spinal cord damage using DTI and evaluate conventional MRI parameters of the spinal cord in HTLV-1-infected individuals.
METHODS
This cross-sectional study involved 33 HTLV-1 carriers, 28 patients with definite-HAM, and 11 seronegative healthy subjects (HS). Region-of-interest (ROI)-based fractional anisotropy (FA) and mean diffusivity (MD) measurements were performed in the upper thoracic and lumbar regions of the spinal cord. Thoracic index was defined as 1/ (anteroposterior diameter × transverse diameter) measured at the fifth 5th vertebral level. Receiver operating characteristic (ROC) curve analysis was used to determine optimal cutoff FA, MD, and thoracic index values.
RESULTS
Spinal cord atrophy was observed in 15 (53.6%) patients with definite-HAM. The area under the ROC curve in the thoracic spinal cord was 0.824 (95% CI, 0.716-0.932), 0.839 (95% CI: 0.736-0.942), and 0.838 (95% CI: 0.728-0.949) for FA, MD, and the thoracic index, respectively. Lower FA and higher MD values were observed in the definite-HAM group compared to HTLV-1 carriers and HS at the T5 vertebral level (p < 0.01).
INTERPRETATION
Complementary to conventional MRI, DTI analysis of the spinal cord and thoracic index determination can offer additional insight that may prove useful in the diagnosis of HAM.
Topics: Atrophy; Benchmarking; Cross-Sectional Studies; Diffusion Tensor Imaging; Humans; Paraparesis, Tropical Spastic
PubMed: 35263043
DOI: 10.1002/acn3.51521 -
Bioscience Reports Mar 2022Human T-cell leukemia virus type 1 (HTLV-1) is the only identified oncogenic human retrovirus. HTLV-1 infects approximately 5-10 million people worldwide and is the... (Review)
Review
Human T-cell leukemia virus type 1 (HTLV-1) is the only identified oncogenic human retrovirus. HTLV-1 infects approximately 5-10 million people worldwide and is the infectious cause of adult T-cell leukemia/lymphoma (ATL) and several chronic inflammatory diseases, including HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), dermatitis, and uveitis. Unlike other oncogenic retroviruses, HTLV-1 does not capture a cellular proto-oncogene or induce proviral insertional mutagenesis. HTLV-1 is a trans-activating retrovirus and encodes accessory proteins that induce cellular transformation over an extended period of time, upwards of several years to decades. Inarguably the most important viral accessory protein involved in transformation is Tax. Tax is a multifunctional protein that regulates several different pathways and cellular processes. This single viral protein is able to modulate viral gene expression, activate NF-κB signaling pathways, deregulate the cell cycle, disrupt apoptosis, and induce genomic instability. The summation of these processes results in cellular transformation and virus-mediated oncogenesis. Interestingly, HTLV-1 also encodes a protein called Hbz from the antisense strand of the proviral genome that counters many Tax functions in the infected cell, such as Tax-mediated viral transcription and NF-κB activation. However, Hbz also promotes cellular proliferation, inhibits apoptosis, and disrupts genomic integrity. In addition to viral proteins, there are other cellular factors such as MEF-2, superoxide-generating NAPDH oxidase 5-α (Nox5α), and PDLIM2 which have been shown to be critical for HTLV-1-mediated T-cell transformation. This review will highlight the important viral and cellular factors involved in HTLV-1 transformation and the available in vitro and in vivo tools used to study this complex process.
Topics: Adult; Basic-Leucine Zipper Transcription Factors; Human T-lymphotropic virus 1; Humans; LIM Domain Proteins; Microfilament Proteins; NF-kappa B; Paraparesis, Tropical Spastic; Retroviridae Proteins; Viral Proteins
PubMed: 35169839
DOI: 10.1042/BSR20211921 -
Cureus Mar 2023Lumbosacral plexopathy (LSP) encompasses a group of disorders affecting post-ganglionic fibers derived from the L1-S4 roots. The differential diagnosis is challenging...
Lumbosacral plexopathy (LSP) encompasses a group of disorders affecting post-ganglionic fibers derived from the L1-S4 roots. The differential diagnosis is challenging and includes other neuropathies of medullary, radicular, or peripheral origin. Defining the etiology is equally crucial, as LSP management relies on its cause. A thorough clinical history should address potential neoplastic disease (new-onset, progression, or relapse), diabetes mellitus, lumbar or pelvic trauma, and previous exposure to radiation. This is the case of a 78-year-old male, with a history of prostatic adenocarcinoma, treated with image-guided radiation therapy and hormone therapy five years before, with no evidence of relapse on follow-up. The patient presented with bilateral weakness, numbness, and paresthesia of lower limbs, gradually progressing over a three-month period, and followed by an acute worsening with inability to stand or walk. He also referred to distal mild edema, episodic hematuria, and urinary incontinence. Physical examination revealed paraparesis affecting proximal and distal leg muscles, along with bilateral hypoesthesia, impaired deep tendon reflexes, and proprioception below knee level. Pelvic, dorsal, and lumbosacral MRI excluded neoplastic lesions but identified somatic fracture of L5 without medullary or conus medullaris compromise. These findings did not explain the clinical picture. Further neurophysiologic studies characterized sensory-motor deficits as post-ganglionic, with specific spontaneous discharges of the muscle fibers, known as myokymia. These findings were consistent with radiation-induced LSP and were supported by MRI. Radiation-induced cystitis was also documented in pelvic MRI and urethral cystoscopy. This case highlights the clinical picture and differential diagnosis of radiation-induced LSP. Despite more typical symptoms and course, a neoplastic origin should always be carefully investigated and excluded. Radiation protocol should be carefully accessed, and its complications should not be overlooked, as they might cause severe morbidity.
PubMed: 37123691
DOI: 10.7759/cureus.36842 -
Viruses Apr 2022HTLV-1 uveitis (HU) is the third clinical entity to be designated as an HTLV-1-associated disease. Although HU is considered to be the second-most frequent... (Review)
Review
HTLV-1 uveitis (HU) is the third clinical entity to be designated as an HTLV-1-associated disease. Although HU is considered to be the second-most frequent HTLV-1-associated disease in Japan, information on HU is limited compared to that on adult T-cell leukemia/lymphoma (ATL) and HTLV-1-associated myelopathy (HAM). Recent studies have addressed several long-standing uncertainties about HU. HTLV-1-related diseases are known to be caused mainly through vertical transmission (mother-to-child transmission), but emerging HTLV-1 infection by horizontal transmission (such as sexual transmission) has become a major problem in metropolitan areas, such as Tokyo, Japan. Investigation in Tokyo showed that horizontal transmission of HTLV-1 was responsible for HU with severe and persistent ocular inflammation. The development of ATL and HAM is known to be related to a high provirus load and hence involves a long latency period. On the other hand, factors contributing to the development of HU are poorly understood. Recent investigations revealed that severe HU occurs against a background of Graves' disease despite a low provirus load and short latency period. This review highlights the recent knowledge on HU and provides an update on the topic of HU in consideration of a recent nationwide survey.
Topics: Adult; Female; HTLV-I Infections; Human T-lymphotropic virus 1; Humans; Infectious Disease Transmission, Vertical; Paraparesis, Tropical Spastic; Proviruses; Uveitis
PubMed: 35458524
DOI: 10.3390/v14040794 -
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