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 The Role of Hbz in Htlv 1 Biology written by Joshua E. Arnold and published by . This book was released on 2008 with total page 165 pages. Available in PDF, EPUB and Kindle. Book excerpt: Abstract: Human T-cell leukemia virus type 1 (HTLV-1) is a pathogenic retrovirus that has the capacity to transform primary human T-lymphocytes in culture and infected individuals. After nearly 30 years of research, the exact mechanism by which HTLV-1 induces cellular transformation and ultimately disease still remains elusive. Tax has been identified as the major viral determinant and is essential to the HTLV-1-mediated T-cell transformation process. The HTLV-1 accessory proteins p12, p13, and p30 are dispensable in culture, but are required for the maintenance of viral loads in vivo. In this dissertation, we sought to broaden our knowledge of HTLV-1 using in vitro culture assays and two animal model approaches focusing our efforts on understanding the contribution of a novel antisense encoded gene, the HTLV-1 basic leucine zipper factor (Hbz), in virus biology. Chapter 1 reviewed important aspects of HTLV-1 pathobiology and highlighted insightful comparative studies between HTLV-1 and HTLV-2. Our work in Chapter 2 determined that the HBZ protein is dispensable for immortalization/transformation of T-lymphocytes in culture, but is required for efficient infectivity and persistence in inoculated rabbits. In Chapter 3, utilizing Hbz-specific short hairpin RNA lentiviral vectors, we showed that Hbz significantly contributed to tumor formation and neoplastic cell spread in the NOG mouse transplant model. Chapter 4 expanded on Chapter 3 to show that Hbz functions in two molecular forms, mRNA and protein, to synergistically increase cell proliferation in vitro. Collectively our results indicate that the Hbz gene negativly regulates Tax-mediated viral gene expression and dysrupts the cellular microenviroment to ultimately support virus survival. The data in this dissertation have allowed us to better understand the contribution of Hbz to HTLV-1 infection, and its involvement in the development of disease.
Download or read book Molecular Analysis of Htlv 2 Aph 2 in Viral Transformation Persistence and Host Immune Response written by Han Yin and published by . This book was released on 2011 with total page 149 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 two closely related human retroviruses but they display distinct differences in pathogenicity. HTLV-1 causes adult T-cell leukemia (ATL) and HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP), whereas HTLV-2 appears much less pathogenic without conclusive disease association. Chapter 1 reviews important aspects of HTLV-1 pathobiology and highlights insightful comparative studies between HTLV-1 and HTLV-2. Chapter 2 and chapter 3 focus on APH-2, the antisense protein of HTLV-2, which shares functional homology to HTLV-1 HBZ as a negative viral regulator. In chapter 2, we investigated the contribution of APH-2 to HTLV-2-mediated immortalization of primary T-lymphocytes in vitro and HTLV-1 infection in a rabbit animal model. HTLV-2 APH-2 mutant viruses were generated and evaluated for viral gene expression, protein production, and immortalization capacity. In short-term proliferation and long-term immortalization assays, APH-2 mutant viruses were indistinguishable from wild-type HTLV-1 suggesting that APH-2 is dispensable for viral replication and cellular immortalization in culture. Rabbits inoculated with irradiated cells expressing HTLV-2 APH-2 mutant viruses became persistently infected. In addition, these rabbits displayed an increased antibody response to viral gene products and a higher proviral load in PBMCs as compared to wild type HTLV-2 infected animals. These observations indicate that APH-2 is not required for viral survival and persistence in vivo during the early stage of infection, which is contrary to what has been observed for HTLV-1 HBZ. To broaden our knowledge of the contribution of antisense proteins to HTLV biology, in chapter 3 we further examined the role of APH-2 and HBZ in regulating the host immune response. We found that both APH-2 and HBZ can potentially reduce type I interferon (IFN) production by inhibiting IFN regulatory factor 7 (IRF-7)-mediated gene transcription. This result indicates that HTLV-1 and HTLV-2 have evolved a common way to antagonize host immune attack upon viral infection. Chapter 4 focuses on the cellular tropism of HTLV-1 and HTLV-2 during the early stage after infection. In vivo, CD4+ T cells are the primary target cells for HTLV-1 in ATL patients even though CD8+ T cells serve as a natural reservoir in HAM/TSP patients and asymptomatic carriers. The HTLV-2 proviral burden has been shown to be higher in CD8+ T cells than in CD4+ T cells in infected individuals. Since most individuals are chronically infected at the time of detection, the early T cell preference of HTLV-1 and HTLV-2 in an immunocompetent host is not known. In chapter 4, we utilized the rabbit animal model to measure the early HTLV-1 and HTLV-2 proviral loads and gene expression patterns in purified CD4+ and CD8+ T cells over time. Our data indicate that the viruses do not exhibit cellular preference during the initial infection stage and the preferential transformation tropism is probably due to a selective clonal expansion during the clinical latency period. Collectively, the data presented in this thesis provides insights into the regulation of HTLV gene expression and the mechanism of cellular transformation and host-virus interplay.
Download or read book Characterization of the Human T cell Leukemia Virus Type 2 P28 Accessory Protein written by Rami Doueiri and published by . This book was released on 2012 with total page 175 pages. Available in PDF, EPUB and Kindle. Book excerpt: Abstract: Human T-cell leukemia virus type 1 (HTLV-1) causes malignancy, several neurodegenerative and inflammatory diseases. On the other hand, HTLV-2 is less pathogenic with few cases of neurodegenerative diseases. Comparative studies of the regulatory genes of HTLV elucidated the role of these proteins in the viral life cycle and in part explained the different pathology of both viruses. However, increasing amount of evidence describes an essential role for the accessory genes in viral pathogenesis. The accessory protein p30 of HTLV-1 and p28 of HTLV-2 are encoded from ORF-II and share some amino acid homology. They are post-transcriptional negative regulators of viral replication, and act by retaining tax/rex mRNA in the nucleus. However, unlike p30, p28 is devoid of transcriptional activity. Several binding proteins, functional domains and post-translational modification have been identified for p30; however, no such studies have been performed for p28. Identification and characterization of p28 structure/function would facilitate comparative studies between p28 and p30, allow us to better understand the role of accessory genes in the viral life cycle, and ultimately to better understand the different pathobiology of HTLV-1 and HTLV-2. In Chapter 2, we identified binding partners of p30 and p28 using mass spectrometry, and then verified our data using molecular methods. We identified NIP30 as a unique binding partner for p30, while hnRNP H1 solely interacted with p28, and PRMT5 interacted with both proteins. We then knocked down PRMT5 in vivo to assess its role in the viral life cycle. Our data suggest that PRMT5 is involved in post-transcriptional control of HTLV-2 replication, while its effect on HTLV-1 might be at the level of DNA damage and cell cycle control. In Chapter 3, we identified and characterized the effect of phosphorylation on p28 in vivo. We conducted phosphoryl mapping of mammalian-expressed p28 protein using mass spectrometry and substitution mutational analysis. We identified seven phosphorylation events on p28 at Ser-33, Ser-160, Ser-170, Ser-172, Thr-199, Ser-200 and Ser-203. We evaluated the functional significance of these phosphorylation sites and found that phosphorylation at Ser-160 and Thr-199 reduced the ability of p28 to dimerize, while phosphorylation did not affect the post-transcriptional activity of p28 or its ability to interact with hnRNP H1 or PRMT5. In Chapter 4, we identified functional domains of p28. We created six p28 deletion mutations p28d"N (deletion of amino acid (aa) (d")1-50), p28d"M1(d"51-100), p28d"M2 (d"101-150), p28d"C (d"151-216), p28d"M2-C (d"101-216) and p28d"M1-M2-C(d"51-216), and evaluated the functional significance of these domains. We identified a tripartite nuclear localization sequence (NLS) in regions N-M2-C (aa 1-50 and 100-216), while p28 interaction with hnRNP H1 requires domains N (aa 1-50) and C (aa 151-216), and its dimerization requires domains M1 (aa 51-100) and C (aa 151-216). Finally, we identified that p28 C terminus (150-216) exerts an inhibitory effect on p28 post-transcriptional function. This work is the first to identify p28 binding partners, phosphorylation sites and functional domains, providing insight into p28 mechanism of action to better understand its role in HTLV-2 replication and pathogenesis.
Download or read book Comparative Studies on Molecular Mechanisms Utilized by HTLV 1 and HTLV 2 in Viral Replication and Induction of T cell Transformation written by Li Xie 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 (HTLV)-1 and HTLV-2 are closely related human retroviruses that have similar genetic organization and biological properties. However, they display distinct pathogenicity. HTLV-1 has been identified as a causal agent for two human diseases, adult T-cell leukemia (ATL) and HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP), whereas HTLV-2 appears much less pathogenic without conclusive disease association. In order to understand the distinct pathogenicity between HTLV-1 and HTLV-2, studies in this dissertation manipulate viral elements in the context of full-length proviral clones, analyze their function and mechanism of action in a system closely mimicking in vivo HTLV infection, and focus on the unique strategies employed by HTLV-1 and/or HTLV-2 to replicate and induce cellular transformation, the initial stage of HTLV oncogenesis. First, our results indicate that the PDZ domain binding motif (PBM) uniquely present in HTLV-1 viral oncoprotein Tax, but absent in HTLV-2 Tax, plays a key role in HTLV-1-induced cell proliferation and genetic instability in vitro and facilitate viral spread and persistence in vivo. Next, we identified a major viral determinant of HTLV T-cell transformation tropism, the envelope, using recombinant proviral clones between HTLV-1 and HTLV-2. Lastly, viral trans-regulatory protein Rex facilitates efficient viral replication and its functional activity is regulated by phosphorylation events. A c-terminal phosphorylation domain (CTPD) has been previously described in HTLV-2 Rex. Here mutational analyses indicate that either introducing phosphomimetic amino acids into the CTPD or deletion of the CTPD can lock Rex in active state. However, HTLV-2 with Rex phosphomimetic mutants, but not HTLV-2 with Rex CTPD deletion mutants, can efficiently infect and stimulate cellular proliferation and immortalization of human primary T-cell, implying the critical role of the Rex CTPD in HTLV-2 life cycle. Overall, our studies provide important insight into the distinct molecular pathogenesis of HTLV-1 and HTLV-2.
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 Comparative Pathology Bulletin written by and published by . This book was released on 1987 with total page 84 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Human Cancer Viruses written by John Nicholas and published by Karger Medical and Scientific Publishers. This book was released on 2008-01-01 with total page 257 pages. Available in PDF, EPUB and Kindle. Book excerpt: The first identification of a tumor-causing virus, Rous sarcoma virus, occurred almost 100 years ago, but it was not until the 1970s that the genetic basis for oncogenesis by this and other acutely transforming retroviruses was appreciated. Since then, numerous viral oncogenes and their corresponding cellular proto-oncogene counterparts have been identified, and these studies have contributed much to our understanding of crucially important aspects of cell biology and transformation.This book provides an up-to-date overview of the 6 major viruses that cause human cancers - HPV, HBV, HCV, EBV, KSHV and HTLV-1 - with respect to their molecular biology and epidemiology and to clinical aspects of disease, therapy and prevention. Contributed by over a dozen internationally renowned scientists, the chapters are comprehensively written and illustrated. The book is suitable for advanced students, postdoctoral researchers, scientists and clinicians who wish to understand the mechanisms leading to cellular transformation and oncogenesis by these viruses as a basis for the development of specific therapeutic and antiviral treatments.
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 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 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 Screening Donated Blood for Transfusion transmissible Infections written by World Health Organization and published by World Health Organization. This book was released on 2010 with total page 73 pages. Available in PDF, EPUB and Kindle. Book excerpt: "Blood transfusion is a life-saving intervention that has an essential role in patient management within health care systems. All Member States of the World Health Organization (WHO) endorsed World Health Assembly resolutions WHA28.72 (1) in 1975 and WHA58.13 (2) in 2005. These commit them to the provision of adequate supplies of safe blood and blood products that are accessible to all patients who require transfusion either to save their lives or promote their continuing or improving health." --Preface.
Download or read book Human Retrovirology written by William A. Blattner and published by Raven Press (ID). This book was released on 1990 with total page 520 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Cytokine Storm Syndrome written by Randy Q. Cron and published by Springer Nature. This book was released on 2019-09-09 with total page 607 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cytokine Storm Syndromes, including HLH and MAS, are frequently fatal disorders, particularly if not recognized early and treated during presentation. The genetics of Cytokine Storm Syndromes are being defined with many of the risk alleles giving rise to mutations in the perforin-mediated cytolytic pathway used by CD8 cytotoxic T cells and natural killer cells. These are being studied using murine models. Up to 10% of the general population may carry risk alleles for developing Cytokine Storm Syndromes, and Cytokine Storm Syndromes are being increasingly recognized around the world in pediatric and adult hospitals. A variety of infectious, rheumatic, and oncologic triggers are commonly associated with Cytokine Storm Syndromes, but understanding this disorder is critical for all researchers and physicians to ensure timely and appropriate therapy. This textbook, the first of its kind, addresses all aspects of the disorder – from genetics, pathophysiology, and ongoing research, to clinical presentations, risk factors, and treatment.
Download or read book Viral Oncology written by George Klein and published by . This book was released on 1980 with total page 874 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Dermatology in Public Health Environments written by Renan Rangel Bonamigo and published by Springer. This book was released on 2018-01-26 with total page 1581 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides a reference guide in the field of dermatology, presenting and discussing its interface with public health. Dermatological diseases are extremely common in populations around the globe, and the systematization of knowledge about these dermatoses and their relationships with different epidemiological factors may help us to understand the challenges that governments and private institutions face and must try to overcome in order to improve global health. Undergraduate and graduate students, dermatologists and general practitioners who study and / or work in the area will find scientific support in this book, which is intended as a reference work for dermatological practice and public health. The book has ten sections addressing carefully selected topics, including: 1. concepts in dermatoepidemiology and the international strategies in programs of Public Health; 2-6. the most significant skin diseases (including dermatology in tropical medicine) ; 7. diseases that are not primarily dermatological, but have a high impact on public health and may have skin and mucosal manifestations; 8. a number of emerging issues in dermatology in public health; 9. clinical approaches (diagnosis and management) to common dermatological symptoms and 10. multidisciplinary approaches in dermatology. The editors have brought together authors with extensive experience in their respective fields in order to provide a reference book for those involved in or with an interest in the relationship between dermatology and public health.
