Download or read book Kinetic Analysis of Human T cell Leukemia Virus Type 1 Gene Expression written by Min Li and published by . This book was released on 2008 with total page 170 pages. Available in PDF, EPUB and Kindle. Book excerpt: Abstract: Human T-cell leukemia virus type 1 (HTLV-1) and type 2 (HTLV-2) are closely related human retroviruses that transform T lymphocytes in cell culture and persist in infected individuals. HTLV-1 infection is clearly associated with leukemia/lymphoma and neurological disease, whereas HTLV-2 disease association is less compelling. HTLV replication and survival requires the expression of multiple gene products from an unspliced and a series of highly related alternatively spliced mRNA species. To date, the levels of viral gene expression throughout the process of infection, cellular transformation, and pathogenesis have not been experimentally assessed. We posit that having a concise viral gene expression profile will provide important insight into the function of specific viral genes and their role in the biology and pathogenesis of HTLV-1.

Download or read book Human T cell leukemia virus 1 HTLV 1 infection associated pathology and response of the host written by Roberto S. Accolla and published by Frontiers Media SA. This book was released on 2023-06-30 with total page 248 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Molecular Analysis of Human T cell Leukemia Virus Regulatory and Accessory Proteins written by Ihab H. Younis and published by . This book was released on 2005 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Abstract: Human T-cell leukemia virus type 1 (HTLV-1) and type 2 (HTLV-2) are closely related pathogenic human retroviruses. Although, they both transform human primary T cells in vitro, in humans, HTLV-1 is the causative agent for ATLL and HAM/TSP, whereas HTLV-2 disease association is less clear. In this dissertation, we report molecular studies regarding the regulation of HTLV replication and its impact on viral persistence in vivo. In Chapter 2, we generate a novel HTLV-1 clone (H1IT) in which the two regulatory proteins, Tax and Rex, have been separated in an attempt to provide a better reagent to study mutants of these proteins in the context of the provirus and analyze their contribution to HTLV-mediated transformation. In vitro data indicates that H1IT is replication competent and is capable of cellular transformation of primary human T-cells. However, H1IT was unable to persist in vivo, emphasizing the importance of temporal and quantitative regulation of Tax RNA to viral replication. In Chapter 3, we report that both HTLV-1 and HTLV-2 have evolved accessory genes whose products are able to restrict viral replication at a post-transcriptional level. The HTLV-1 p30 and the related HTLV-2 p28 proteins inhibit both Tax and Rex by binding to and retaining tax/rex mRNA in the nucleus, thereby inhibiting virion production. In Chapter 4, we show that p28 is recruited to the viral promoter in a Tax-dependent manner. After recruitment to the promoter, p28 or p30 travels with the transcription elongation machinery until its target mRNA is synthesized. Since the above data is consistent with a critical role of these accessory proteins in viral persistence in vivo, in Chapter 5, we used an animal model of HTLV infection to study the specific contribution of p28 on HTLV-2 survival. In this study, all wtHTLV-2 infected rabbits showed persistent infection, whereas those infected with HTLV-2[delta]p28 were able to eliminate the virus as early as 2 weeks, indicating that p28 is critical for early viral infectivity, spread and/or persistence in rabbits. Collectively, data presented within this dissertation support the conclusion that the regulation of HTLV gene expression a complicated but a tightly controlled process.

Download or read book Study of the Regulation of the Human T Cell Leukemia Virus Type 1 HTLV 1 Promoter Formatted in the Context of Chromatin in T Cells and Monocytes written by Devanshi Pandya and published by . This book was released on 2007 with total page 152 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Regulation of Human T cell Leukemia Virus Type 1 Infection and Replication written by Gunjan Choudhary and published by . This book was released on 2010 with total page 156 pages. Available in PDF, EPUB and Kindle. Book excerpt: Retroviruses have evolved complex mechanisms to regulate their cellular tropism and gene expression. It is generally accepted that productive infections proceed via interactions between viral envelope molecules and specific receptors on the host cell surface. Currently, there is no known receptor for HTLV-1, though a number of factors that enhance entry have been identified. In an effort to identify a cellular receptor or attachment factor for HTLV-1, we carried out a retroviral cDNA library screen, in which cDNA from permissive HeLa S3 cells was introduced into poorly susceptible NIH 3T3 cells. These cells were selected after infection with HTLV-1 envelope pseudotyped viral particles expressing a drug resistance gene. We isolated approximately 460 cDNAs, of which 20 were prioritized as potential candidates. These candidates are being tested to determine if they participate in viral entry. In addition to encoding the structural and enzymatic genes common to all retroviruses, HTLV-1 also encodes several accessory genes which contribute to viral replication and the maintenance of gene expression. A newly identified viral gene, HTLV-1 bZIP factor or hbz, has been shown to have pleiotropic effects as it functions differently in its protein and mRNA forms. In an effort to elucidate its role in HTLV-1 replication, we identified a novel function. Mutations that abrogated the hbz mRNA or disrupted a stem-loop in hbz mRNA, or mutations that eliminated or truncated the HBZ protein were introduced in a functional molecular clone of HTLV-1. The protein and stem-loop mutants had no effect on viral gene expression. However, the mutant that disrupted hbz mRNA expressed lower levels of tax mRNA, suggesting that hbz promotes tax expression. We found that this effect of hbz was indirect, as hbz represses another accessory gene, p30II, which is known to sequester tax mRNA in the nucleus. These results provide new insights into the regulation of HTLV-1 infection, specifically viral entry and gene expression.

Download or read book Transformation Studies of Human T cell Leukemia Virus with Emphasis on the Role of Tax and Rex written by Jianxin Je and published by . This book was released on 2003 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Abstract: HTLV-1 and HTLV-2 both transform human primary T cells but the precise transformation mechanism remains to be elucidated. We studied two HTLV regulatory proteins, Tax and Rex, and their role in HTLV-mediated cellular transformation. HTLV-1 has a preferential transformation tropism of CD4+ T cells, whereas HTLV-2 transforms primarily CD8+ T cells. Since Tax is critical for cellular transformation and differences have been identified between Tax-1 and Tax-2, we hypothesize that the viral determinant of transformation tropism is encoded by Tax. Using molecular clones of HTLV-1 (Ach) and HTLV-2 (pH6neo) we constructed recombinants in which Tax and overlapping Rex genes of the two viruses were exchanged. p19 Gag expression from proviral clones transfected into 293T cells indicated that both recombinants contained functional Tax and Rex but with significantly altered activity as compared to the wild-type clones. Stable transfectants expressing recombinant viruses were established, irradiated, and cocultured with peripheral blood mononuclear cells (PBMC). Both recombinants were competent to transform T-lymphocytes with efficiency similar to the parental viruses. Flow cytometry analysis indicated that HTLV-1 and HTLV-1/TR2 had a preferential tropism for CD4+ T cells and HTLV-2 and HTLV-2/TR1 had a preferential tropism for CD8+ T cells. Our results indicate that tax/rex in different genetic backgrounds display altered functional activity but ultimately do not contribute to the different in vitro transformation tropism. We also studied the contribution of Rex in HTLV-1-mediated immortalization of primary T-cells in vitro and viral survival in a rabbit animal model. Our results provide the first direct evidence that Rex and its function to modulate viral gene expression and virion production is not required for in vitro immortalization by HTLV-1. However, Rex is critical for efficient infection of cells and persistence in vivo. Efficient HTLV replication requires Rex/RxRE regulation of incompletely spliced viral mRNAs that encode the viral enzymatic and structural proteins. Overall, our results indicate that post-transcriptional control elements identified in other viruses have a partial capacity to substitute for HTLV Rex/RxRE function, although the low activities of these elements are insufficient to maintain viral replication and virus spread in culture. Together this work provides important information on the role of Tax and Rex on HTLV replication and cellular transformation and further insight into the biological differences between HTLV-1 and HTLV-2.

Download or read book Two Decades of Adult T cell Leukemia and HTLV I Research written by Kazuo Sugamura and published by S. Karger AG (Switzerland). This book was released on 2003 with total page 394 pages. Available in PDF, EPUB and Kindle. Book excerpt: In April 2001, the Japanese Cancer Association was privileged to host a symposium in Kyoto to commemorate the twentieth anniversary of the discovery of the viral pathogenesis of adult T-cell leukemia (ATL). In this monograph, the editors have selected not only papers presented at the symposium but also eminent papers of several individuals from around the world who have extensively researched human T-cell-leukemia virus type I (HTLV-I), the etiological virus of ATL, over the years. During the last two decades, HTLV-I was molecularly characterized as harboring a variety of oncogenic properties in its Tax protein. Epidemiological studies not only revealed the existence of HTLV-I-endemic areas in the world, but also disclosed the routes of transmission. Despite these great strides, the mechanisms of ATL development have not yet been fully clarified, and viable therapeutic measures are still to be established. This monograph contains recent exciting achievements in molecular virology, epidemiology, immunology and therapeutic trials as well as historical profiles of HTLV-I and HTLV-I-associated diseases.

Download or read book Mechanisms of Tax Regulation of Human T cell Leukemia Virus Type I Gene Expression written by Audrey A. Franklin and published by . This book was released on 1995 with total page 312 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Comparative studies between HTLV 1 and HTLV 2 function and pathobiology written by Umberto Bertazzoni and published by Frontiers Media SA. This book was released on 2015-06-11 with total page 95 pages. Available in PDF, EPUB and Kindle. Book excerpt: Human T-cell leukemia viruses type 1 and 2 (HTLV-1 and HTLV-2) share a common genetic organization, expression strategy and ability to infect and immortalize T-cells in vitro; however, HTLV-1 and HTLV-2 are strikingly different in terms of clinical impact. HTLV-1 is recognized as the aetiological agent of adult T-cell leukemia/lymphoma (ATLL), and HTLV-associated myeolopathy/tropical spastic paraparesis (HAM/TSP), in contrast, HTLV-2 does not cause hematologic disorders and is only sporadically associated with cases of subacute myelopathy. HTLV-1 and HTLV-2 also exhibit distinct cellular tropisms in vivo: HTLV-1 is mainly found in CD4+T lymphocytes, whereas CD8+T-cells are the preferred target for HTLV-2. The articles contributed in this Research Topic are covering all the different aspects that characterize HTLV-1 and HTLV-2, by highlighting differences in their biology that might provide clues to their distinct pathogenic properties.

Download or read book Molecular Pathology of HTLV 1 written by Umberto Bertazzoni and published by Frontiers Media SA. This book was released on 2019-03-25 with total page 225 pages. Available in PDF, EPUB and Kindle. Book excerpt: Human T-cell leukemia virus type 1 (HTLV-1) was the first human retrovirus discovered, in 1980, by Gallo and co-workers. About 5-10% of HTLV-1-infected individuals are at risk of developing either a fatal malignancy, adult T-cell leukemia (ATL), or a chronic neuroinflammatory syndrome, HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Both diseases are incurable at present. Many issues concerning HTLV-1’s life cycle and pathobiology are still unsolved or controversial, and new approaches for prognostic stratification of patients and eradication of HTLV-1 infection are in high demand. In this Research Topic, the focus has been centered on discussing two main themes: the functional analysis and oncogenic potential of HTLV-1 regulatory proteins and the control of HTLV-1-associated diseases. The 22 articles in this eBook cover many different aspects of HTLV-1 infection and pathogenesis, providing new perspectives and groundwork for future studies.

Download or read book Role of Human T lymphotropic Virus Type 1 P30 II and Surface Envelope as Determinants of in Vivo Pathogenesis written by Lee Silverman and published by . This book was released on 2005 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Abstract: Human T-cell leukemia virus type 1 (HTVL-1) is the first identified human retrovirus. In addition to gag, pol, and env genes, HTLV-1 contains four open reading frames (ORF) within its pX region. ORF II encodes p30II and p13II. Herein, we determine the in vivo significance of p30II by inoculating rabbits with cell lines expressing either a wild-type clone of HTLV-1 (ACH. 1) or a p30II mutant clone (ACH. 30.1). Compared to ACH. 1 rabbits, ACH. 30.1 rabbits had lower antibody titers, a smaller percentage of seropositive animals, a smaller percentage of animals with provirus in peripheral blood mononuclear cells (PBMC), and lower proviral loads. Sequencing revealed that provirus in ACH. 30.1 provirus positive rabbits had reverted to wild-type sequence. We conclude that there is strong selective pressure for expression of p30II in vivo. We next sought to determine if p30II modulates cellular apoptosis. A greater percentage of ACH. 30.1 cells were induced into apoptosis compared to ACH. 1 cells following treatment with camptothecin (specific for S-phase of cell cycle). There was no difference in apoptosis induction between ACH. 30.1 and ACH. 1 cells following treatment with etoposide (intrinsic pathway) or TRAIL (extrinsic pathway). p30II did not modulate susceptibility to apoptosis when expressed in 293T cells or in Jurkat T cells. Expression of p30II in Jurkat T cells reduced cell proliferation by delaying onset of division. Although p30II does not modulate susceptibility to apoptosis, it does reduce cell proliferation. HTLV-1 Env Ser75Ile, Asn95Asp, and Asn195Asp mutants are able to immortalize lymphocytes in vitro. Herein, we examine the effects of these mutations in rabbits via inoculations with ACH. 75, ACH. 95, ACH. 195, and ACH. 1 cell lines. All mutations were maintained in vivo. ACH. 75 and ACH. 95 rabbits had decreased antibody responses to Gag and Env. One ACH. 195 rabbit had an antibody response to HTLV-1 proteins and HTLV-2 Env. Another ACH. 195 rabbit had provirus in PBMC but no serologic response. ACH. 195 rabbits had a diminished antibody response to Env surface (SU) protein. PBMC proviral loads did not correlate with antibody response to SU. These mutations in HTLV-1 Env SU alter proviral loads and antibody responses against Env but do not prevent virus replication in vivo.

Download or read book Structure and Function Studies of Human T Lymphotrophic Virus Type 1 written by Nadine Yvonne Bowden and published by . This book was released on 2011 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Abstract: The complex retrovirus human T-lymphotrophic virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia (ATL) and a variety of inflammatory disorders. Only about 5% of infected individuals develop ATL and then only after a 30 to 50 year clinical latency period. Reasons for this are incompletely understood. Viral modulation of viral and cellular protein expression is thought to be a major contributor to the phenomenon. HTLV-1 Tax has a prominent role in modulation activities. Key Tax activities include altering cellular response to DNA damage, apoptosis signals, and cell cycle regulation. However, expression of Tax and some Tax modulated activities increase the probability of the virus being detected and eliminated by the immune system. The virus mediates this risk by employing other viral proteins to modulate the activities and effects of Tax. HTLV-1 p30 (p30), the focus of this thesis, is one of the viral proteins that provides a counter balance to the activities of Tax. p30 selectively retains tax mRNA in the nucleus, competes with Tax for limited transcriptional elements and transcriptionally regulates both HTLV-1 and cellular gene expression. Improving our understanding of how p30 accomplishes these activities will improve our ability to combat HTLV-1 infections. Critical to understanding the mechanisms of action of p30 is knowledge of which amino acid residues and post-translational modifications are required for the functions of p30. In chapter 2, we used bioinformatics analysis to predict motifs and post-translational modifications of p30. Our bioinformatics studies revealed 11 highly conserved serines, all predicted to be phosphorylated. To test the presence of phosphorylation we used P32 labeling and mass spectrometry. Mass spectrometry revealed two serines at positions 88 and 102 that were phosphorylated. In chapter 3 we explored the impact of p30 on expression of a subset of genes associated with cellular response to DNA damage. Two complementary, but different methods were utilized to assay mRNA expression; RT2 Profiler PCR Array and NanoString. We also evaluated the impact of p30 on gene expression in the presence and absence of DNA damage. Our data indicate that p30 selectively impacts gene expression patterns and furthermore the pattern of expression is altered by the presence of DNA damage. In chapter 4, we extended our NanoString based gene expression study from chapter 3. Our chapter 3 study showed expression levels of 5 genes in the DNA damage pathway, GML, XRCC6, ATRX, CDK7 and GTF2H2, were altered in a statistically significant fashion in the presence of p30 following induction of DNA damage. Using Ingenuity Pathway Analysis (IPA) we explored hypotheses to explain changes in expression of the group as a unit and of the individual genes. Our exploration led us to focus on XRCC6 because it is implicated in repression of the HTLV-1 LTR and the G2/M cell cycle checkpoint, two areas in which there are established roles for p30. Our data has introduced two viable venues to further explore the details of the functions of p30, the role of phosphorylation and the impact of decreased expression of XRCC6.

Download or read book Inducible Gene Expression Volume 1 written by P.A. Baeuerle and published by Springer Science & Business Media. This book was released on 2013-12-01 with total page 294 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cells have evolved multiple strategies to adapt the composition and quality of their protein equipment to needs imposed by changes in intra- and extracellular conditions. The appearance of pro teins transmit ting novel functional properties to cells can be controlled at a transcrip tional, posttranscriptional, translational or posttranslational level. Extensive research over the past 15 years has shown that transcriptional regulation is used as the predominant strategy to control the production of new proteins in response to extracellular stimuli. At the level of gene transcription, the initiation ofmRNA synthesis is used most frequently to govern gene expression. The key elements controlling transcription initiation in eukaryotes are activator proteins (transactivators) that bind in a sequence-specific manner to short DNA sequences in the of genes. The activator binding sites are elements of larger proximity control units, ca lied promoters and enhancers, which bind many distinct proteins. These may synergize or negatively cooperate with the activators. The do novo binding of an activator to DNA or, if already bound to DNA, its functional activation is what ultimately turns on a high-level expression of genes. The activity of transactivators is controlled by signalling pathways and, in some cases, transactivators actively partici pate in signal transduction by moving from the cytoplasm into the nuc1eus. In this first volume of Inducible Gene Expression, leading scientists in the field review six eukaryotic transactivators that allow cells to respond to various extracellular stimuli by the expression of new proteins.

Download or read book Prevention and Control of Human T Lymphotropic Viruses 1 and 2 HTLV 1 2 written by Ricardo Ishak and published by Frontiers Media SA. This book was released on 2022-09-22 with total page 323 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book HTLV 1 Addressing Unmet Research Needs written by Louis M. Mansky and published by Frontiers Media SA. This book was released on 2021-05-20 with total page 209 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Recent Advances In Human Retroviruses Principles Of Replication And Pathogenesis Advances In Retroviral Research written by Kuan-teh Jeang and published by World Scientific. This book was released on 2010-07-29 with total page 502 pages. Available in PDF, EPUB and Kindle. Book excerpt: There are three major types of human retroviruses, namely HIV, HTLV, and endogenous human retroviruses. This book presents the latest findings on the replication of these human retroviruses. This book is unique in that there has been no comparable book that integrates the findings from the three known classes of human retroviruses. Other books have focused on one of the three classes of human retroviruses individually.An accomplished international team of contributing authors have combined their expertise to provide cutting-edge findings in this important field. The book will be a valuable reference for students, researchers and medical professionals.

Download or read book Human Herpesviruses written by Ann Arvin and published by Cambridge University Press. This book was released on 2007-08-16 with total page 1325 pages. Available in PDF, EPUB and Kindle. Book excerpt: This comprehensive account of the human herpesviruses provides an encyclopedic overview of their basic virology and clinical manifestations. This group of viruses includes human simplex type 1 and 2, Epstein–Barr virus, Kaposi's Sarcoma-associated herpesvirus, cytomegalovirus, HHV6A, 6B and 7, and varicella-zoster virus. The viral diseases and cancers they cause are significant and often recurrent. Their prevalence in the developed world accounts for a major burden of disease, and as a result there is a great deal of research into the pathophysiology of infection and immunobiology. Another important area covered within this volume concerns antiviral therapy and the development of vaccines. All these aspects are covered in depth, both scientifically and in terms of clinical guidelines for patient care. The text is illustrated generously throughout and is fully referenced to the latest research and developments.