During HTLV-1 infection, the virus integrates into the host cell genome as a provirus with a single CCCTC binding protein (CTCF) binding site (vCTCF-BS), which acts as an insulator between transcriptionally active and inactive regions. Previous studies have shown that the vCTCF-BS is important for maintenance of chromatin structure, regulation of viral expression, and DNA and histone methylation. Here, we show that the vCTCF-BS also regulates viral infection and pathogenesis in a humanized (Hu) mouse model of adult T-cell leukemia/lymphoma.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
March 2024
Human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus responsible for adult T-cell leukemia/lymphoma, a severe and fatal CD4+ T-cell malignancy. Additionally, HTLV-1 can lead to a chronic progressive neurodegenerative disease known as HTLV-1-associated myelopathy/tropical spastic paraparesis. Unfortunately, the prognosis for HTLV-1-related diseases is generally poor, and effective treatment options are limited.
View Article and Find Full Text PDFHTLV-1 is an oncogenic human retrovirus and the etiologic agent of the highly aggressive ATL malignancy. Two viral genes, and , are individually linked to oncogenic transformation and play an important role in the pathogenic process. Consequently, regulation of HTLV-1 gene expression is a central feature in the viral lifecycle and directly contributes to its pathogenic potential.
View Article and Find Full Text PDFHuman T-cell leukemia virus type 1 (HTLV-1) is the etiologic cause of adult T-cell leukemia/lymphoma (ATL) and encodes a viral oncoprotein (Hbz) that is consistently expressed in asymptomatic carriers and ATL patients, suggesting its importance in the development and maintenance of HTLV-1 leukemic cells. Our previous work found Hbz protein is dispensable for virus-mediated T-cell immortalization but enhances viral persistence. We and others have also shown that hbz mRNA promotes T-cell proliferation.
View Article and Find Full Text PDFBackground: Iatrogenic Cushing's syndrome is commonly seen as a complication of chronic steroid use. While most often associated with the use of prescription oral steroids, rare cases result from unintentional steroid exposure. In particular, numerous complementary and alternative medicines have been found to contain steroids not previously known to users.
View Article and Find Full Text PDFThe complex retrovirus, human T-cell leukemia virus type 1 (HTLV-1), primarily infects CD4+ T-cells in vivo. Infectious spread within this cell population requires direct contact between virally-infected and target cells. The HTLV-1 accessory protein, HBZ, was recently shown to enhance HTLV-1 infection by activating intracellular adhesion molecule 1 (ICAM-1) expression, which promotes binding of infected cells to target cells and facilitates formation of a virological synapse.
View Article and Find Full Text PDFHuman T-cell leukemia virus type 1 (HTLV-1) is the infectious cause of adult T-cell leukemia/lymphoma (ATL), an extremely aggressive and fatal malignancy of CD4 T-cells. Due to the chemotherapy-resistance of ATL and the absence of long-term therapy regimens currently available for ATL patients, there is an urgent need to characterize novel therapeutic targets against this disease. Protein arginine methyltransferase 5 (PRMT5) is a type II PRMT enzyme that is directly involved in the pathogenesis of multiple different lymphomas through the transcriptional regulation of relevant oncogenes.
View Article and Find Full Text PDFHuman T-cell leukemia virus type 1 (HTLV-1) is an oncogenic retrovirus. Of the approximate ten to twenty million people currently infected worldwide, 4-9% of infected individuals develop adult T-cell leukemia/lymphoma (ATLL) or HTLV-associated myelopathy/tropical spastic paresis (HAM/TSP) in their lifetime. The current report is based on a patient who presented concurrently with CD30+ lymphoma subtype ATLL and HAM/TSP.
View Article and Find Full Text PDFEngineering signalling between plants and microbes could be exploited to establish host-specificity between plant-growth-promoting bacteria and target crops in the environment. We previously engineered rhizopine-signalling circuitry facilitating exclusive signalling between rhizopine-producing (RhiP) plants and model bacterial strains. Here, we conduct an in-depth analysis of rhizopine-inducible expression in bacteria.
View Article and Find Full Text PDFHuman T-cell leukemia virus type 1 (HTLV-1) is the causative infectious agent of adult T-cell leukemia/lymphoma (ATL) and chronic neurological disease. The disparity between silenced sense transcription versus constitutively active antisense (Hbz) transcription from the integrated provirus is not fully understood. The presence of an internal viral enhancer has recently been discovered in the Tax gene near the 3' long terminal repeat (LTR) of HTLV-1.
View Article and Find Full Text PDFBackground: Negative symptoms are typically observed in people with schizophrenia and indicate a loss or reduction of normal function (e.g. reduced motivation and affect display).
View Article and Find Full Text PDFEngineering N2-fixing symbioses between cereals and diazotrophic bacteria represents a promising strategy to sustainably deliver biologically fixed nitrogen (N) in agriculture. We previously developed novel transkingdom signaling between plants and bacteria, through plant production of the bacterial signal rhizopine, allowing control of bacterial gene expression in association with the plant. Here, we have developed both a homozygous rhizopine producing (RhiP) barley line and a hybrid rhizopine uptake system that conveys upon our model bacterium Azorhizobium caulinodans ORS571 (Ac) 103-fold improved sensitivity for rhizopine perception.
View Article and Find Full Text PDFAdult T-cell leukemia/lymphoma (ATL) is an aggressive T-cell lymphoproliferative malignancy caused by human T-cell leukemia virus type 1 (HTLV-1). ATL is an orphan disease with no curative drug treatment regimens urgently needing new combination therapy. HTLV-1-infected cells rely on viral proteins, Tax and HBZ (HTLV-1-b-ZIP factor), to activate the transcription of various host genes that are critical for promoting leukemic transformation.
View Article and Find Full Text PDFMol Plant Microbe Interact
December 2021
An mutant (OPS0865) unable to make poly-3-hydroxybutyrate (PHB), grows poorly on many carbon sources and cannot fix nitrogen in laboratory culture. However, when inoculated onto its host plant, , mutant consistently fixed nitrogen. Upon reisolation from root nodules, a suppressor strain (OPS0921) was isolated that has significantly improved growth on a variety of carbon sources and also fixes nitrogen in laboratory culture.
View Article and Find Full Text PDFAdult T-cell leukemia/lymphoma (ATLL) is an aggressive T-cell malignancy with a poor prognosis with current therapy. Here we report genome-wide CRISPR-Cas9 screening of ATLL models, which identified CDK6, CCND2, BATF3, JUNB, STAT3, and IL10RB as genes that are essential for the proliferation and/or survival of ATLL cells. As a single agent, the CDK6 inhibitor palbociclib induced cell cycle arrest and apoptosis in ATLL models with wild-type TP53.
View Article and Find Full Text PDFBackground/Purpose Oesophageal Atresia (OA) is associated with co-existent anomalies. There is a controversy of literature pertaining to the risk (s) of intestinal malrotation. In order to guide management we critically evaluate the incidence of IM anomalies in OA newborns.
View Article and Find Full Text PDFHuman T-cell leukemia virus type 1 (HTLV-1) is a retrovirus that causes an aggressive T-cell malignancy and a variety of inflammatory conditions. The integrated provirus includes a single binding site for the epigenomic insulator, CCCTC-binding protein (CTCF), but its function remains unclear. In the current study, a mutant virus was examined that eliminates the CTCF-binding site.
View Article and Find Full Text PDFAbstractSensory systems are predicted to be adapted to the perception of important stimuli, such as signals used in communication. Prior work has shown that female zebra finches perceive the carotenoid-based orange-red coloration of male beaks-a mate choice signal-categorically. Specifically, females exhibited an increased ability to discriminate between colors from opposite sides of a perceptual category boundary than equally different colors from the same side of the boundary.
View Article and Find Full Text PDFFront Cell Infect Microbiol
June 2021
CRISPR editing of retroviral proviruses has been limited to HIV-1. We propose human T-cell leukemia virus type 1 (HTLV-1) as an excellent model to advance CRISPR/Cas9 genome editing technologies against actively expressing and latent retroviral proviruses. HTLV-1 is a tumorigenic human retrovirus responsible for the development of both leukemia/lymphoma (ATL) and a neurological disease (HAM/TSP).
View Article and Find Full Text PDFBackground And Aims: Recent studies suggest that long-term endurance training may be damaging to the heart, thus increasing cardiovascular disease (CVD) risk. However, studies utilizing cardiac imaging are conflicting and lack measures of central and peripheral vascular structure and function, which are also independently predictive of CVD events.
Methods: We performed a comprehensive assessment of cardiovascular structure and function in long-term (≥ 10 years) ultra-endurance athletes (ATH, 14 M/11 F, 50 ± 1 y) and physically active controls (CON, 9 M/9 F, 49 ± 2 y).
Animals often use assessment signals to communicate information about their quality to a variety of receivers, including potential mates, competitors, and predators. But what maintains reliable signaling and prevents signalers from signaling a better quality than they actually have? Previous work has shown that reliable signaling can be maintained if signalers pay fitness costs for signaling at different intensities and these costs are greater for lower quality individuals than higher quality ones. Models supporting this idea typically assume that continuous variation in signal intensity is perceived as such by receivers.
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