Integrated Epigenetic Mapping of Human and Mouse Salivary Gene Regulation.

Significant effort has been applied to identify the genome-wide gene expression profiles associated with salivary gland development and pathophysiology. However, relatively little is known about the regulators that control salivary gland gene expression. We integrated data from DNase1 digital genomic footprinting, RNA-seq, and gene expression microarrays to comprehensively characterize the cis- and trans-regulatory components controlling gene expression of the healthy submandibular salivary gland.

[Inhibition of proliferation of adult T-cell leukemia cells by celastrol].

We studied the effect of celastrol on the proliferation and apoptosis of adult T-cell leukemia (ATL) cells. After treating adult T-cell leukemia cell lines with different concentrations of celastrol, we analyzed the cell proliferation by MTT and colony formation assays. Flow cytometry was conducted to detect cell apoptosis by Annexin V-FITC/PI staining.

-mRNA-Carrying Exosomes from Human T Cell Lymphotropic Virus Type 1-Infected Cells Can Induce Interferon-Gamma Production .

Human T cell lymphotropic virus type 1 (HTLV-1) is the etiological agent of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T cell leukemia/lymphoma. The development of HAM/TSP, a chronic neuroinflammatory disease, is correlated to complex interaction between the host immune response and the infecting virus. Tax expression plays an important role in HAM/TSP pathogenesis by activating various cellular genes, including the cytokines interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α).

The clinical impact of human T-lymphotrophic virus type 1 (HTLV-1) infection on the development of adult T-cell leukemia-lymphoma (ATL) or HTLV-1-associated myelopathy (HAM) / atypical HAM after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and renal transplantation.

Because there are limited clinical reports on the impact of human T-lymphotropic virus type 1 (HTLV-1) on organ transplantation, its effects on the development of adult T-cell leukemia-lymphoma (ATL), post-transplantation lymphoproliferative disorder (PTLD) and HTLV-1-associated myelopathy (HAM) or atypical HAM after organ transplantation remain unclear.We retrospectively analyzed the impact of HTLV-1 in 54 allogeneic hematopoietic stem cell transplantation (allo-HSCT) cases and 31 renal transplantation cases between January 2006 and December 2016.Among the 54 allo-HSCT cases, nine recipients with ATL tested positive for HTLV-1, and one was found to be an HTLV-1 carrier.

Droplet digital PCR for absolute quantification of proviral load of human T-cell lymphotropic virus (HTLV) types 1 and 2.

Background: Human T-lymphotrophic virus (HTLV) types 1 and 2 cause lifelong infection whereby most infected individuals are asymptomatic whilst a minority develop infection-related disease. These latter patients invariably have been found to have high proviral load (PVL). Therefore, infected patients are monitored by determining the proportion of lymphocytes that are infected with HTLV-1/2.

FOXP3-positive T-cell lymphomas in non-HTLV1 carriers include ALK-negative anaplastic large cell lymphoma: expanding the spectrum of T-cell lymphomas with regulatory phenotype.

Forkhead box P3 (FOXP3) is a specific marker for regulatory T-cells (Tregs). We report 6 cases of T-cell lymphomas with Treg phenotype based on diffuse positivity for FOXP3 in tumor cells. The patients showed a median age of 56 years with a male predominance.

The Human T-Cell Leukemia Virus Type 1 Basic Leucine Zipper Factor Attenuates Repair of Double-Stranded DNA Breaks via Nonhomologous End Joining.

Adult T-cell leukemia (ATL) is a fatal malignancy of CD4 T cells infected with human T-cell leukemia virus type 1 (HTLV-1). ATL cells often exhibit random gross chromosomal rearrangements that are associated with the induction and improper repair of double-stranded DNA breaks (DSBs). The viral oncoprotein Tax has been reported to impair DSB repair but has not been shown to be consistently expressed throughout all phases of infection.

HTLV-1, ATLL, refractory hypercalcaemia and HIV-1 co-infection.

Adult T-cell lymphoma/leukemia (ATLL) is a rare tumour of T-lymphocytes that is associated with human T-lymphotrophic virus type 1 (HTLV-1) infection as well as severe/refractory hypercalcaemia. Human immunodefficiency virus type 1 (HIV-1) infected individuals are at increased risk of acquiring co-infection with HTLV-1. We present the case of a 37 -year -old HIV-1 positive and antiretroviral therapy naive woman who was admitted to the ICU with delirium, a generalised maculopapular rash, severe hypercalcaemia of 4.

Hypertrophic spinal pachymeningitis associated with human T-cell lymphotrophic virus-1 infection and Sjogren's syndrome: A case report and brief literature review.

Introduction: Reports of hypertrophic spinal pachymeningitis associated with human T-cell lymphotrophic virus-1 (HTLV-1) infection and Sjogren's syndrome in the English literature are still very rare.

Presentation Of Case: We hereby present a case of a 78-year-old female with a history of lower extremity weakness after a fall, which fully resolved after conservative treatment. However, the symptoms recurred 4 years later, and the patient became unable to walk.

Unexpected donor-derived infectious transmissions by kidney transplantation: A systematic review.

Background: Unexpected donor-derived transmission of infections is rare, but is associated with significant morbidity and mortality. We aimed to provide an overview of published cases on unexpected infectious transmissions.

Methods: We systematically reviewed all published evidence describing any unexpected donor-derived viral, bacterial, fungal, and parasitic infections in kidney transplant recipients.

HTLV-1 Tax plugs and freezes UPF1 helicase leading to nonsense-mediated mRNA decay inhibition.

Up-Frameshift Suppressor 1 Homolog (UPF1) is a key factor for nonsense-mediated mRNA decay (NMD), a cellular process that can actively degrade mRNAs. Here, we study NMD inhibition during infection by human T-cell lymphotropic virus type I (HTLV-1) and characterise the influence of the retroviral Tax factor on UPF1 activity. Tax interacts with the central helicase core domain of UPF1 and might plug the RNA channel of UPF1, reducing its affinity for nucleic acids.

Sporadic on/off switching of HTLV-1 Tax expression is crucial to maintain the whole population of virus-induced leukemic cells.

Viruses causing chronic infection artfully manipulate infected cells to enable viral persistence in vivo under the pressure of immunity. Human T-cell leukemia virus type 1 (HTLV-1) establishes persistent infection mainly in CD4+ T cells in vivo and induces leukemia in this subset. HTLV-1-encoded Tax is a critical transactivator of viral replication and a potent oncoprotein, but its significance in pathogenesis remains obscure due to its very low level of expression in vivo.

Interference of HTLV-1 Tax Protein with Cell Polarity Regulators: Defining the Subcellular Localization of the Tax-DLG1 Interaction.

Human T cell leukemia virus (HTLV)-1 Tax (Tax) protein is very important in viral replication and cell transformation. Tax localizes in the nucleus and cytoplasm in association with organelles. Some activities of Tax depend on interactions with PDZ (PSD-95/Discs Large/Z0-1) domain-containing proteins such as Discs large protein 1 (DLG1) which is involved in cell polarity and proliferation.

Adult T-Cell Leukemia/Lymphoma.

Adult T-cell lymphoma/leukemia (ATL) is a rare T-cell lymphoproliferative neoplasm caused by human T-lymphotrophic virus 1. In its more common, aggressive forms, ATL carries one of the poorest prognoses of the non-Hodgkin lymphomas. The disease has clinical subtypes (ie, acute, lymphoma, chronic, and smoldering forms) defined by the presenting features, and therefore, the clinical course can vary.

Extrafollicular activities: perspectives on HIV infection, germinal center-independent maturation pathways, and KSHV-mediated lymphoproliferation.

Early events in the pathogenesis of KSHV-associated lymphoproliferations in the context of HIV disease remain poorly understood. Recent research indicates that latent HIV infection causes persistent immune dysfunction in B cell follicles. Simultaneously, lack of T cell immune surveillance in the lymph nodes dysregulates the biology of EBV.

Hijacking of the O-GlcNAcZYME complex by the HTLV-1 Tax oncoprotein facilitates viral transcription.

The viral Tax oncoprotein plays a key role in both Human T-cell lymphotropic virus type 1 (HTLV-1)-replication and HTLV-1-associated pathologies, notably adult T-cell leukemia. Tax governs the transcription from the viral 5'LTR, enhancing thereby its own expression, via the recruitment of dimers of phosphorylated CREB to cAMP-response elements located within the U3 region (vCRE). In addition to phosphorylation, CREB is also the target of O-GlcNAcylation, another reversible post-translational modification involved in a wide range of diseases, including cancers.

A Unique T-Cell Receptor Amino Acid Sequence Selected by Human T-Cell Lymphotropic Virus Type 1 Tax-Specific Cytotoxic T Cells in HLA-A24:02-Positive Asymptomatic Carriers and Adult T-Cell Leukemia/Lymphoma Patients.

We previously reported that the T-cell receptor (TCR) repertoire of human T-cell lymphotropic virus type 1 (HTLV-1) Tax-specific CD8 cytotoxic T cells (Tax-CTLs) was highly restricted and a particular amino acid sequence motif, the PDR motif, was conserved among HLA-A*24:02-positive (HLA-A*24:02) adult T-cell leukemia/lymphoma (ATL) patients who had undergone allogeneic hematopoietic cell transplantation (allo-HSCT). Furthermore, we found that donor-derived PDR CTLs selectively expanded in ATL long-term HSCT survivors with strong CTL activity against HTLV-1. On the other hand, the TCR repertoires in Tax-CTLs of asymptomatic HTLV-1 carriers (ACs) remain unclear.

HTLV-1-induced leukotriene B4 secretion by T cells promotes T cell recruitment and virus propagation.

The human T-lymphotropic virus type 1 (HTLV-1) is efficiently transmitted through cellular contacts. While the molecular mechanisms of viral cell-to-cell propagation have been extensively studied in vitro, those facilitating the encounter between infected and target cells remain unknown. In this study, we demonstrate that HTLV-1-infected CD4 T cells secrete a potent chemoattractant, leukotriene B4 (LTB4).

Expression of HTLV-1 Genes in T-Cells Using RNA Electroporation.

Human T-cell leukemia virus type 1 (HTLV-1) infects about 20 million people world-wide. Around 5% of the infected individuals develop adult T-cell leukemia (ATL) or a neurological disease termed tropical spastic paraparesis (TSP) after a clinical latency of years to decades. Through the use of two promoters and alternative splicing HTLV-1 expresses at least 12 different proteins.