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The Lancet. Infectious Diseases Jan 2021Human T-cell lymphotropic virus type-1 (HTLV-1) has a large global burden and in some key communities, such as Indigenous Australians living in remote areas, greater... (Review)
Review
Human T-cell lymphotropic virus type-1 (HTLV-1) has a large global burden and in some key communities, such as Indigenous Australians living in remote areas, greater than 45% of people are infected. Despite HTLV-1 causing serious malignancy and myelopathic paraparesis, and a significant association with a range of inflammatory comorbidities and secondary infections that shorten lifespan, few biomedical interventions are available. HTLV-1 starkly contrasts with other blood-borne sexually transmitted viral infections, such as, HIV, hepatitis B virus, and hepatitis C virus, with no antiviral treatments that reduce virus-infected cells, no rapid diagnostics or biomarker assays suitable for use in remote settings, and no effective vaccine. We review how the replication strategies and molecular properties of HTLV-1 establish a long-term stealthy viral pathogenesis through a fine-tuned balance of persistence, immune cell dysfunction, and proliferation of proviral infected cells that collectively present robust barriers to treatment and prevention. An understanding of the nature of the HTLV-1 provirus and opposing actions of viral-coded negative-sense HBZ and positive-sense regulatory proteins Tax, p12 and its cleaved product p8, and p30, is needed to improve the biomedical tools for preventing transmission and improving the long-term health of people with this lifelong infection.
Topics: Australia; Gene Expression Regulation, Viral; HTLV-I Infections; Host-Pathogen Interactions; Human T-lymphotropic virus 1; Humans; Recurrence; T-Lymphocytes
PubMed: 32986997
DOI: 10.1016/S1473-3099(20)30328-5 -
Retrovirology Feb 2020HTLV-1 was the first described human retrovirus and was soon found to be associated with severe clinical diseases, including a devastating lymphoma/leukemia and other... (Review)
Review
HTLV-1 was the first described human retrovirus and was soon found to be associated with severe clinical diseases, including a devastating lymphoma/leukemia and other inflammatory diseases. Although HTLV-2 is not usually pathogenic, it is widely distributed among native Indian populations in Brazil, particularly in the Amazon region of the country. Presently, HTLV spreads mainly by the sexual route and from mother to child, and virus persistence is an active biological factor aiding its transmission. Recently, the use of illicit drugs has been shown to be an additional risk factor, showing the influence of new habits on the epidemiology of HTLV in the region. Despite the detection of the virus in several different populations in the Amazon region of Brazil for almost 30 years, the exact prevalence of HTLV-1/2 is not well defined. The original biases in sampling and the selection of epidemiologically unsuitable populations were commonly repeated in most prevalence studies, generating unreliable and conflicting figures that do not represent the actual prevalence of HTLV. The improvements in clinical and laboratory facilities have resulted in the description of several clinical manifestations that were previously unknown in the region. The extent of the spread of the virus must be defined in this region, which is the largest geographical area of the country. As prophylaxis advances toward the use of vaccines against HTLV-1, it is important to determine who is at risk of being infected and developing a disease to successfully implement preventive measures, particularly as proposals are made to eradicate the virus among humans.
Topics: Brazil; Female; HTLV-I Infections; Human T-lymphotropic virus 1; Humans; Infectious Disease Transmission, Vertical; Phylogeny; Prevalence
PubMed: 32059740
DOI: 10.1186/s12977-020-0512-z -
Viruses Oct 2021Bovine leukaemia virus (BLV) is a deltaretrovirus that is closely related to human T-cell leukaemia virus types 1 and 2 (HTLV-1 and -2). It causes enzootic bovine... (Review)
Review
Bovine leukaemia virus (BLV) is a deltaretrovirus that is closely related to human T-cell leukaemia virus types 1 and 2 (HTLV-1 and -2). It causes enzootic bovine leukosis (EBL), which is the most important neoplastic disease in cattle. Most BLV-infected cattle are asymptomatic, which potentiates extremely high shedding rates of the virus in many cattle populations. Approximately 30% of them show persistent lymphocytosis that has various clinical outcomes; only a small proportion of animals (less than 5%) exhibit signs of EBL. BLV causes major economic losses in the cattle industry, especially in dairy farms. Direct costs are due to a decrease in animal productivity and in cow longevity; indirect costs are caused by restrictions that are placed on the import of animals and animal products from infected areas. Most European regions have implemented an efficient eradication programme, yet BLV prevalence remains high worldwide. Control of the disease is not feasible because there is no effective vaccine against it. Therefore, detection and early diagnosis of the disease are essential in order to diminish its spreading and the economic losses it causes. This review comprises an overview of bovine leukosis, which highlights the epidemiology of the disease, diagnostic tests that are used and effective control strategies.
Topics: Animals; Cattle; Diagnostic Tests, Routine; Enzootic Bovine Leukosis; Female; Genome, Viral; Human T-lymphotropic virus 1; Leukemia Virus, Bovine; Prevalence; Virulence
PubMed: 34834973
DOI: 10.3390/v13112167 -
The Lancet. Infectious Diseases Oct 2018
Topics: Australia; Biomedical Research; HTLV-I Infections; Human T-lymphotropic virus 1; Humans
PubMed: 30303105
DOI: 10.1016/S1473-3099(18)30561-9 -
Cellular Microbiology Oct 2018In order to thrive, viruses have evolved to manipulate host cell machinery for their own benefit. One major obstacle faced by pathogens is the immunological synapse. To... (Review)
Review
In order to thrive, viruses have evolved to manipulate host cell machinery for their own benefit. One major obstacle faced by pathogens is the immunological synapse. To enable efficient replication and latency in immune cells, viruses have developed a range of strategies to manipulate cellular processes involved in immunological synapse formation to evade immune detection and control T-cell activation. In vitro, viruses such as human immunodeficiency virus 1 and human T-lymphotropic virus type 1 utilise structures known as virological synapses to aid transmission of viral particles from cell to cell in a process termed trans-infection. The formation of the virological synapse provides a gateway for virus to be transferred between cells avoiding the extracellular space, preventing antibody neutralisation or recognition by complement. This review looks at how viruses are able to subvert intracellular signalling to modulate immune function to their advantage and explores the role synapse formation has in viral persistence and cell-to-cell transmission.
Topics: Gap Junctions; HIV-1; Human T-lymphotropic virus 1; Humans; Immunological Synapses; Lymphocyte Activation; T-Lymphocytes; Virus Replication
PubMed: 30123959
DOI: 10.1111/cmi.12944 -
Current Opinion in Virology Oct 2017Human T-lymphotropic virus type-1 (HTLV-1) is the causative agent of adult T-cell leukaemia/lymphoma (ATL), an aggressive CD4+ T-cell malignancy. The mechanisms of... (Review)
Review
Human T-lymphotropic virus type-1 (HTLV-1) is the causative agent of adult T-cell leukaemia/lymphoma (ATL), an aggressive CD4+ T-cell malignancy. The mechanisms of leukaemogenesis in ATL are incompletely understood. Insertional mutagenesis has not previously been thought to contribute to the pathogenesis of ATL. However, the recent discovery that HTLV-1 binds the key chromatin architectural protein CTCF raises the hypothesis that HTLV-1 deregulates host gene expression by causing abnormal chromatin looping, bringing the strong HTLV-1 promoter-enhancer near to host genes that lie up to 2Mb from the integrated provirus. Here we review current opinion on the mechanisms of oncogenesis in ATL, with particular emphasis on the local and distant impact of HTLV-1 on the structure and expression of the host genome.
Topics: CCCTC-Binding Factor; Host-Pathogen Interactions; Human T-lymphotropic virus 1; Humans; Leukemia-Lymphoma, Adult T-Cell; Mutagenesis, Insertional; Protein Binding; Proviruses
PubMed: 28822906
DOI: 10.1016/j.coviro.2017.07.013 -
Retrovirology Dec 2019The human T cell leukemia virus type 1 (HTVL-1), first reported in 1980 by Robert Gallo's group, is the etiologic agent of both cancer and inflammatory diseases. Despite... (Review)
Review
The human T cell leukemia virus type 1 (HTVL-1), first reported in 1980 by Robert Gallo's group, is the etiologic agent of both cancer and inflammatory diseases. Despite approximately 40 years of investigation, the prognosis for afflicted patients remains poor with no effective treatments. The virus persists in the infected host by evading the host immune response and inducing proliferation of infected CD4 T-cells. Here, we will review the role that viral orf-I protein products play in altering intracellular signaling, protein expression and cell-cell communication in order to escape immune recognition and promote T-cell proliferation. We will also review studies of orf-I mutations found in infected patients and their potential impact on viral load, transmission and persistence. Finally, we will compare the orf-I gene in HTLV-1 subtypes as well as related STLV-1.
Topics: CD4-Positive T-Lymphocytes; Cell Proliferation; HTLV-I Infections; Human T-lymphotropic virus 1; Humans; Immune Evasion; Paraparesis, Tropical Spastic; Simian T-lymphotropic virus 1; Viral Load; Viral Regulatory and Accessory Proteins
PubMed: 31852543
DOI: 10.1186/s12977-019-0502-1 -
Viruses Jan 2022Human T-cell leukemia virus type 1 (HTLV-1) is an oncogenic retrovirus that is the causative infectious agent of adult T-cell leukemia/lymphoma (ATL), an aggressive and... (Review)
Review
Human T-cell leukemia virus type 1 (HTLV-1) is an oncogenic retrovirus that is the causative infectious agent of adult T-cell leukemia/lymphoma (ATL), an aggressive and fatal CD4 T-cell malignancy, and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a chronic neurological disease. Disease progression in infected individuals is the result of HTLV-1-driven clonal expansion of CD4 T-cells and is generally associated with the activities of the viral oncoproteins Tax and Hbz. A closely related virus, HTLV-2, exhibits similar genomic features and the capacity to transform T-cells, but is non-pathogenic. In vitro, HTLV-1 primarily immortalizes or transforms CD4 T-cells, while HTLV-2 displays a transformation tropism for CD8 T-cells. This distinct tropism is recapitulated in infected people. Through comparative studies, the genetic determinant for this divergent tropism of HTLV-1/2 has been mapped to the viral envelope (Env). In this review, we explore the emerging roles for Env beyond initial viral entry and examine current perspectives on its contributions to HTLV-1-mediated disease development.
Topics: CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cell Transformation, Viral; Gene Products, env; Gene Products, tax; Human T-lymphotropic virus 1; Human T-lymphotropic virus 2; Humans; Leukemia-Lymphoma, Adult T-Cell; Oncogenes; Virus Internalization
PubMed: 35062342
DOI: 10.3390/v14010138 -
Retrovirology May 2020Human T cell leukemia virus type-1 (HTLV-1) was the first retrovirus found to cause cancer in humans, but the mechanisms that drive the development of leukemia and other... (Review)
Review
Human T cell leukemia virus type-1 (HTLV-1) was the first retrovirus found to cause cancer in humans, but the mechanisms that drive the development of leukemia and other diseases associated with HTLV-1 infection remain to be fully understood. This review describes the functional properties of p13, an 87-amino acid protein coded by HTLV-1 open reading frame II (orf-II). p13 is mainly localized in the inner membrane of the mitochondria, where it induces potassium (K) influx and reactive oxygen species (ROS) production, which can trigger either proliferation or apoptosis, depending on the ROS setpoint of the cell. Recent evidence indicates that p13 may influence the cell's innate immune response to viral infection and the infected cell phenotype. Association of the HTLV-1 transcriptional activator, Tax, with p13 increases p13's stability, leads to its partial co-localization with Tax in nuclear speckles, and reduces the ability of Tax to interact with the transcription cofactor CBP/p300. Comparison of p13 sequences isolated from HTLV-1-infected individuals revealed a small number of amino acid variations in the domains controlling the subcellular localization of the protein. Disruptive mutations of p13 were found in samples obtained from asymptomatic patients with low proviral load. p13 sequences of HTLV-1 subtype C isolates from indigenous Australian patients showed a high degree of identity among each other, with all samples containing a pattern of 5 amino acids that distinguished them from other subtypes. Further characterization of p13's functional properties and sequence variants may lead to a deeper understanding of the impact of p13 as a contributor to the clinical manifestations of HTLV-1 infection.
Topics: Animals; Genetic Variation; Human T-lymphotropic virus 1; Humans; Open Reading Frames; Retroviridae Proteins
PubMed: 32398094
DOI: 10.1186/s12977-020-00517-1 -
Biological Trace Element Research Sep 2021Human T cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP), as the most common neurological emersion related to HTLV-1, is...
Human T cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP), as the most common neurological emersion related to HTLV-1, is a debilitating and lifelong treating disease with no definitive treatment. Furthermore, it has been determined that dietary compositions (inflammatory and anti-inflammatory) and some micronutrients (such as vitamin D and selenium) have an effect on inflammatory and immune processes and with this background; the study was done to compare the nutritional status between age- and sex-matched with infected and non-infected HTLV-1. In a multi-center setting, 70 healthy controls (HCs), 35 asymptomatic carriers (ACs), and 35 HAM/TSP patients were recruited in the HTLV-1 Foundation, Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran. Nutritional status including anthropometric indices, dietary (micro- and macronutrient) intake, and serum vitamin D, vitamin B12, zinc, and selenium were measured. In anthropometric indices, mean waist circumference (WC) in the carrier group was significantly higher than the patient and the control groups (p = 0.008). In the dietary intake, the patient group received less energy, protein, mono-unsaturated fatty acids (MUFA), and oleic, but more fat than the HTLV-1 carrier and control groups, and these differences were remarkable in three groups (p = 0.002, 0.005, 0.001, 0.01, and 0.001, respectively), whereas the carrier group received more saturated fatty acid and less poly-unsaturated fatty acids (PUFA), linoleic, and linolenic than patient and control groups with a different significant (p = 0.01, 0.007, 0.005, and 0.006, respectively) in three groups. In micronutrient intake, although selenium, zinc, and vitamins B12 and D were lower in the patient group than the carrier and control group, however, no significant differences were observed. In comparison with micronutrient serum concentrations, vitamins B12 and D and selenium in the patient group were lower than the carrier and control groups, but statistically, the considerable difference was found only in the selenium concentration (p = 0.001). The study showed that there were differences in dietary intake (including energy, macronutrients, and fatty acids), WC, and selenium serum levels between HAM/TSP patients and HTLV-1 carriers, suggesting that nutritional statues influence the inflammatory immune response in HTLV-1 infection.
Topics: Eating; HTLV-I Infections; Human T-lymphotropic virus 1; Humans; Iran; Selenium
PubMed: 33169347
DOI: 10.1007/s12011-020-02472-6