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 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 Mechanism of Human T cell Leukemia Virus Type I Gene HTLV I Regulation as Mediated by Regulatory Protein Tax written by Neeraj Adya and published by . This book was released on 1994 with total page 268 pages. Available in PDF, EPUB and Kindle. Book excerpt:
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 Molecular Analysis of Human T cell Leukemia Virus Type 2 Accessory Protein written by Brenda Michiyo Yamamoto and published by . This book was released on 2009 with total page 162 pages. Available in PDF, EPUB and Kindle. Book excerpt: Abstract: The human T-cell leukemia virus type 1 (HTLV-1) and type 2 (HTLV-2) are two pathogenic retroviruses. Although both viruses share a common genome organization and amino acid homology in common viral proteins, the incidence of disease with infection is distinct. Infection with HTLV-1 may result in the development of adult T-cell leukemia/lymphoma (ATL), an aggressive neoplastic disease, or a variety of immune-mediated/inflammatory disorders such as HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP), whereas HTLV-2 is less pathogenic. Our studies focused on the open reading frame II encoded p28 protein of HTLV-2, which has been shown to negatively regulate viral expression by the nuclear retention of the tax/rex mRNA. A similar post-transcriptional regulatory function has been observed with HTLV-1 ORF-II p30. However, p28 contrasts p30 in that there appears to be no significant transcriptional effects. In Chapter 2, we examined the functional significance of p28 in HTLV-2 infection, proliferation, and immortalization of primary T-cells in culture, and viral infection and survival in a rabbit model of HTLV infection. We generated a novel HTLV-2 p28 termination clone (HTLV2Deltap28) in which a stop codon had been introduced into the p28 sequence without altering the amino acid sequence of the overlapping regulatory proteins, Tax and Rex. In short-term proliferation and long-term immortalization coculture assays, HTLV2Deltap28 infected and immortalized primary human T-cells, similar to wtHTLV-2. However, HTLV2Deltap28 had a lower capacity to establish persistent infection in rabbits, indicating the in vivo importance of HTLV-2 p28. These results are consistent with the hypothesis that p28 repression of Tax and Rex-mediated viral gene expression allows infected cells to avoid immune recognition and elimination, or acts to enhance early viral spread by enhancing the survival of HTLV-2 infected cells. In Chapter 3, we generated and characterized various dual-promoter and single-promoter lentiviral expression vectors. Post-transduction, p28 protein was readily detected with the dual-promoter vectors in 293T cells but not in Jurkat T-cells. The differential p28 protein expression was found to be due to cell-type specific translation mechanisms. To circumvent this problem we utilized a single-promoter lentiviral vector that expresses p28 via the murine stem cell virus (MSCV)-promoter, which resulted in efficient p28 protein expression in both T-cell lines and primary human CD8+ T-lymphocytes. In Chapter 4, the capacity of p28 to modify cellular gene expression was examined. In transient transfection studies, low doses of p28 modulated CRE- and NF[kappa]B-driven reporter constructs in 293T cells, suggesting the ability of p28 in modulating cellular gene expression. Interestingly, transduction of Jurkat T-cells with the lentiviral p28 expression vector had no significant effect on cellular proliferation. Additionally, initial analysis of global cellular gene expression by microarray analysis suggests that p28 results in nominal alterations in cellular gene expression. Collectively, data presented in this thesis indicates that p28 is critical for the establishment and survival of HTLV-2, compatible with the conclusion that the regulation of HTLV gene expression is a tightly controlled and complex process. Ultimately, while minimal, the impact of p28 upon cellular genes likely contributes to HTLV-2 establishment of infection in vivo.
Download or read book T Cell Leukemia written by Olga Babusikova and published by BoD – Books on Demand. This book was released on 2011-10-26 with total page 247 pages. Available in PDF, EPUB and Kindle. Book excerpt: The purpose of this book is to provide a comprehensive review of the scientific advances in T-cell malignancies and to highlight the most relevant findings that will help the reader understand both basic mechanisms of the disease and future directions that are likely to lead to novel therapies. In order to assure a thorough approach to these problems, contributors include basic scientists, translational researchers and clinicians who are experts in this field. Thus, the target audience for this book includes both basic scientists who will use this book as a review of the advances in our fundamental knowledge of the molecular mechanisms of T-cell malignancies, as well as clinicians who will use this book as a tool to understand rationales for the development of novel treatments for these diseases.
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 Subcellular Localization of Human T cell Leukemia Virus Type 1 Tax Oncoprotein written by Kimberly Anne Fryrear and published by . This book was released on 2008 with total page 218 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Viral and Immunological Malignancies written by Paul Volberding and published by PMPH-USA. This book was released on 2006 with total page 440 pages. Available in PDF, EPUB and Kindle. Book excerpt: The precise relationship between viral infection and malignancy remains an epidemiologic association and the subject of active investigation. Nonmalignant hematologic disorders have a similarly complex relationship with cancer-associated viruses and may offer insight into the pathogenesis of oncogenesis. This book explores the relationships between viral infections, immune impairments and the hematologic and malignant diseases, particularly against the backdrop of the HIV epidemic. By extending the scope to all of viral oncology the editors provide an invaluable resource on tumors related to other viruses other than HIV, particularly carcinomas of the cervix and anus with HPV and tumors of the liver with the various hepatitis viruses.
Download or read book The Human T cell Leukemia Virus Type I Tax Protein Represses Gene Expression Through the BHLH Transcription Factors written by Martine Noelle Uittenbogaard and published by . This book was released on 1996 with total page 210 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Molecular Mimicry Infection Inducing Autoimmune Disease written by Michael B. A. Oldstone and published by Springer Science & Business Media. This book was released on 2006-01-09 with total page 166 pages. Available in PDF, EPUB and Kindle. Book excerpt: (Text will follow)
Download or read book Activation of Human T cell Leukemia Virus Gene Expression by Formation of a Complex Between the Transactivator Tax and the Cellular Transcription Factor Creb written by Min-Jean Yin and published by . This book was released on 1996 with total page 448 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Human Retroviruses written by Bryan Cullen and published by Oxford University Press. This book was released on 1993 with total page 220 pages. Available in PDF, EPUB and Kindle. Book excerpt: The first book to specifically cover the molecular biology of retroviruses - of immense importance since the high profile of HIV. International contributors provide detailed reviews of the latest knowledge. An excellent text for both medical and non-medical researchers, it also serves as an illuminating introduction for scientists active in other areas.
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 The Regulation of RNA Processing by the Rex Protein of Human T cell Leukemia Virus Type II written by Andreas Bakker 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 Human T Cell Lymphotropic Virus Type I written by Per Höllsberg and published by John Wiley & Sons. This book was released on 1996-12-02 with total page 352 pages. Available in PDF, EPUB and Kindle. Book excerpt: HTLV is made up of any of several retroviruses including the retrovirus known as AIDS. Devoted to the rapidly growing field of HTLV, this book explores the many different aspects of the virus.
Download or read book Regulation of the P21WAF1 Promoter by Human T Cell Leukemia Virus Type I HTLV I Tax written by Julie Christine Watt and published by . This book was released on 2005 with total page 168 pages. Available in PDF, EPUB and Kindle. Book excerpt:
