Human T-cell leukemia virus type I (HTLV-I) infection and the onset of adult T-cell leukemia (ATL)

The clinical entity of adult T-cell leukemia (ATL) was established around 1977, and human T-cell leukemia virus type 1 (HTLV-I) was subsequently identified in 1980. In the 25 years since the discovery of HTLV-I, HTLV-I infection and its associated diseases have been extensively studied, and many of their aspects have been clarified. However, the detailed mechanism of leukemogenesis remains unsolved yet, and the prognosis of ATL patients still poor because of its resistance to chemotherapy and immunodeficiency. In this review, I highlight the recent progress and remaining enigmas in HTLV-I infection and its associated diseases, especially ATL

Human T-cell leukemia virus type 1: replication, proliferation and propagation by Tax and HTLV-1 bZIP factor.

Human T-cell leukemia virus type 1 (HTLV-1) spreads primarily by cell-to-cell transmission. Therefore, HTLV-1 promotes the proliferation of infected cells to facilitate transmission. In HTLV-1 infected individuals, the provirus is present mainly in effector/memory T cells and Foxp3+ T cells. Recent study suggests that this immunophenotype is acquired by infected cells through the function of HTLV-1 bZIP factor (HBZ). Tax, which is encoded by the plus strand, is crucial for viral replication and de novo infection, while HBZ, encoded by the minus strand, is important for proliferation of infected cells. Importantly, HBZ and Tax have opposing functions in most transcription pathways. HBZ and Tax cooperate in elaborate ways to permit viral replication, proliferation of infected cells and propagation of the virus

Isothermal annealing of a 620 nm optical absorption band in Brazilian topaz crystals

Isothermal decay behaviors, observed at 515, 523, 562, and 693 K, for an optical absorption band at 620 nm in gamma-irradiated Brazilian blue topaz were analyzed using a kinetic model consisting of O- bound small polarons adjacent to recombination centers (electron traps). the kinetic equations obtained on the basis of this model were solved using the method of Runge-Kutta and the fit parameters describing these defects were determined with a grid optimization method. Two activation energies of 0.52 +/- 0.08 and 0.88 +/- 0.13 eV, corresponding to two different structural configurations of the O- polarons, explained well the isothermal decay curves using first-order kinetics expected from the kinetic model. On the other hand, thermoluminescence (TL) emission spectra measured at various temperatures showed a single band at 400 nm in the temperature range of 373-553 K in which the 620 nm optical absorption band decreased in intensity. Monochromatic TL glow curve data at 400 nm extracted from the TL emission spectra observed were found to be explained reasonably by using the knowledge obtained from the isothermal decay analysis. This suggests that two different structural configurations of O- polarons are responsible for the 620 nm optical absorption band and that the thermal annealing of the polarons causes the 400 nm TL emission band. (C) 2013 Elsevier B.V. All rights reserved.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Secretaria de Ciencia e Tecnologia (RHAE)Financiadora de Estudos e Projetos (FINEP)Univ São Paulo, Inst Fis, BR-01498 São Paulo, BrazilUniversidade Federal de São Paulo, São Paulo, BrazilUniversidade Federal de São Paulo, São Paulo, BrazilWeb of Scienc

ATF3, an HTLV-1 bZip factor binding protein, promotes proliferation of adult T-cell leukemia cells

<p>Abstract</p> <p>Background</p> <p>Adult T-cell leukemia (ATL) is an aggressive malignancy of CD4⁺T-cells caused by human T-cell leukemia virus type 1 (HTLV-1). The <it>HTLV-1 bZIP factor </it>(<it>HBZ</it>) gene, which is encoded by the minus strand of the viral genome, is expressed as an antisense transcript in all ATL cases. By using yeast two-hybrid screening, we identified activating transcription factor 3 (ATF3) as an HBZ-interacting protein. ATF3 has been reported to be expressed in ATL cells, but its biological significance is not known.</p> <p>Results</p> <p>Immunoprecipitation analysis confirmed that ATF3 interacts with HBZ. Expression of ATF3 was upregulated in ATL cell lines and fresh ATL cases. Reporter assay revealed that ATF3 could interfere with the HTLV-1 Tax's transactivation of the 5' proviral long terminal repeat (LTR), doing so by affecting the ATF/CRE site, as well as HBZ. Suppressing ATF3 expression inhibited proliferation and strongly reduced the viability of ATL cells. As mechanisms of growth-promoting activity of ATF3, comparative expression profiling of ATF3 knockdown cells identified candidate genes that are critical for the cell cycle and cell death, including cell division cycle 2 (CDC2) and cyclin E2. ATF3 also enhanced p53 transcriptional activity, but this activity was suppressed by HBZ.</p> <p>Conclusions</p> <p>Thus, ATF3 expression has positive and negative effects on the proliferation and survival of ATL cells. HBZ impedes its negative effects, leaving ATF3 to promote proliferation of ATL cells via mechanisms including upregulation of CDC2 and cyclin E2. Both HBZ and ATF3 suppress Tax expression, which enables infected cells to escape the host immune system.</p

Design and synthesis of biotin- or alkyne-conjugated photoaffinity probes for studying the target molecules of PD 404182.

To investigate the mechanism of action of the potent antiviral compound PD 404182, three novel photoaffinity probes equipped with a biotin or alkyne indicator were designed and synthesized based on previous structure-activity relationship studies. These probes retained the potent anti-HIV activity of the original pyrimidobenzothiazine derivatives. In photoaffinity labeling studies using HIV-1-infected H9 cells (H9IIIB), eight potential proteins were observed to bind PD 404182

Systematic clustering algorithm for chromatin accessibility data and its application to hematopoietic cells

The huge amount of data acquired by high-throughput sequencing requires data reduction for effective analysis. Here we give a clustering algorithm for genome-wide open chromatin data using a new data reduction method. This method regards the genome as a string of $1$s and $0$s based on a set of peaks and calculates the Hamming distances between the strings. This algorithm with the systematically optimized set of peaks enables us to quantitatively evaluate differences between samples of hematopoietic cells and classify cell types, potentially leading to a better understanding of leukemia pathogenesis.Comment: 24 pages, 17 figure