DOCSLIB.ORG

Reducing the Global Burden of HTLV-1 Infection: an Agenda for Research and Action

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Reducing the Global Burden of HTLV-1 Infection: an Agenda for Research and Action Antiviral Research 137 (2017) 41e48 Contents lists available at ScienceDirect Antiviral Research journal homepage: www.elsevier.com/locate/antiviral Review Reducing the global burden of HTLV-1 infection: An agenda for research and action * Luc Willems a, z, , Hideki Hasegawa b, z, Roberto Accolla c, Charles Bangham d, Ali Bazarbachi e, Umberto Bertazzoni f, Anna Barbara de Freitas Carneiro-Proietti g, Hua Cheng h, Luigi Chieco-Bianchi i, Vincenzo Ciminale i, Jordana Coelho-dos-Reis j, Jose Esparza h, Robert C. Gallo h, Antoine Gessain k, Eduardo Gotuzzo l, William Hall m, Joseph Harford n, Olivier Hermine o, Steven Jacobson p, Beatrice Macchi q, Calum Macpherson r, Renaud Mahieux s, Masao Matsuoka t, Edward Murphy u, Jean-Marie Peloponese v, Viviana Simon w, Yutaka Tagaya h, Graham P. Taylor d, Toshiki Watanabe x, Yoshihisa Yamano y a University of Liege, Belgium b National Institute of Infectious Diseases, Tokyo, Japan c University of Insubria, Varese, Italy d Imperial College, London, UK e American University of Beirut, Beirut, Lebanon f University of Verona, Verona, Italy g Fundaçao~ Hemominas, Belo Horizonte, Brazil h Institute of Human Virology, Baltimore, USA i University of Padova, Padova, Italy j Rene Rachou Research Center, FIOCRUZ, Belo Brazil Horizonte, Brazil k Institut Pasteur, Paris, France l Tropical Medical Institute Alexander von Humboldt, Lima, Peru m Centre for Research in Infectious Disease, Dublin, Ireland n National Cancer Institute, NIH, Bethesda, USA o Hopital^ Necker, Paris, France p National Institute of Neurological Disorders and Stroke, NIH, Bethesda, USA q University of Rome Tor Vergata, Rome, Italy r St. George's University, Grenada s Ecole Normale Superieure de Lyon, Lyon, France t Kyoto University, Kyoto, Japan u University of California, San Francisco, USA v University of Montpellier, Montpellier, France w Icahn School of Medicine at Mount Sinai, New York, USA x University of Tokyo, Tokyo, Japan y St. Marianna University School of Medicine, Kanagawa, Japan z Chairs of the HTLV Taskforce of the Global Virus Network, USA article info abstract e Article history: Even though an estimated 10 20 million people worldwide are infected with the oncogenic retrovirus, Received 21 October 2016 human T-lymphotropic virus type 1 (HTLV-1), its epidemiology is poorly understood, and little effort has Accepted 29 October 2016 been made to reduce its prevalence. In response to this situation, the Global Virus Network launched a Available online 11 November 2016 taskforce in 2014 to develop new methods of prevention and treatment of HTLV-1 infection and promote basic research. HTLV-1 is the etiological agent of two life-threatening diseases, adult T-cell leukemia and HTLV-associated myelopathy/tropical spastic paraparesis, for which no effective therapy is currently Keywords: HTLV-1 available. Although the modes of transmission of HTLV-1 resemble those of the more familiar HIV-1, Vaccine routine diagnostic methods are generally unavailable to support the prevention of new infections. In * Corresponding author. Molecular and Cellular Epigenetics, Interdisciplinary Cluster for Applied Genoproteomics (GIGA) of University of Liege (ULg), B34, 1 Avenue de l'Hopital,^ 4000, Sart-Tilman, Liege, Belgium. E-mail address: [email protected] (L. Willems). http://dx.doi.org/10.1016/j.antiviral.2016.10.015 0166-3542/© 2016 Elsevier B.V. All rights reserved. 42 L. Willems et al. / Antiviral Research 137 (2017) 41e48 Oncogene the present article, the Taskforce proposes a series of actions to expand epidemiological studies; increase Retrovirus research on mechanisms of HTLV-1 persistence, replication and pathogenesis; discover effective treat- Leukemia ments; and develop prophylactic and therapeutic vaccines. © 2016 Elsevier B.V. All rights reserved. Contents 1. Introduction: the global burden of HTLV-1 infection . ..................... 42 2. The HTLV taskforce . ..................... 42 3. Research priorities and open questions . ..................... 42 3.1. Review the global prevalence of HTLV-1 infection and identify opportunities and means to expand epidemiological studies . ......42 3.2. Identify biomarkers to predict disease progression . ............................45 3.3. Develop preventive and therapeutic vaccines . .......................................45 3.4. Screen for existing and novel drugs to improve therapy . ............................45 3.5. Perform basic research to unravel mechanisms of viral persistence, replication and pathogenesis to open insights into novel treatments . 46 4. Conclusion and perspectives . ..................... 46 Acknowledgements . ...................................................47 References . ...................................................47 1. Introduction: the global burden of HTLV-1 infection (McSweegan et al., 2015). The GVN includes a number of centers of excellence for research in medical virology across the globe. For It is estimated that at least 20 million people worldwide are further information, readers are referred to the GVN website at infected with the oncogenic retrovirus, human T-cell leukemia vi- http://gvn.org. rus type 1 (HTLV-1). The area of highest prevalence is southwestern The HTLV taskforce emerged from an initiative of the GVN on Japan, but infection is also common in sub-Saharan Africa, the June 17, 2014. The members of the HTLV-1 taskforce are located on Caribbean islands, and some regions of South America, the Middle Fig. 1 and listed in Table 1. East and Austro-Melanesia. Similar to the human immunodefi- Consultation among taskforce members has led to the following ciency virus (HIV)-1, transmission occurs principally from mother proposed series of actions to be carried out by researchers in GVN to child, between sexual partners, through contaminated blood centers of excellence and their scientific collaborators: products and by needle sharing. Infected individuals are at risk of developing a rapidly progressive malignancy, adult T-cell leukemia review the global prevalence of HTLV-1 infection and identify (ATL), and a debilitating and sometimes fatal neurologic condition, opportunities and means to expand epidemiological studies; myelopathy/tropical spastic paraparesis (HAM/TSP). In contrast to identify biomarkers to predict disease progression; HIV-1 and beyond screening serology, only limited diagnostic develop prophylactic and therapeutic vaccines; methods are available, generally for research studies, and little screen for existing and novel drugs to improve therapy; effort has been made to identify infected persons and reduce perform basic research to unravel mechanisms of viral infec- transmission. No vaccines or fully effective therapies are currently tivity, persistence, replication and pathogenesis to open insights available. A closely related virus, HTLV-2, is present in many world into novel treatments; areas (e.g. North and South America, South of Europe, Ireland, Vietnam) and its pathogenic potential needs to be further clarified. These proposed actions are discussed in turn in the following In response to this situation, the Global Virus Network launched sections. a taskforce in 2014 to promote basic research, develop new methods of prevention and treatment of HTLV-1 infection and recommend new public health measures. This article presents the 3. Research priorities and open questions consensus views of taskforce members regarding unsolved or controversial issues that hamper further understanding of HTLV-1 3.1. Review the global prevalence of HTLV-1 infection and identify and the development of new approaches for diagnosis, preven- opportunities and means to expand epidemiological studies tion and therapy. For additional information on the molecular mechanisms of pathogenesis, immunological aspects, epidemi- Regions of high prevalence, including Indonesia, Iran, Africa, ology and currently available therapies for HTLV-1 infection, Japan, the Caribbean, South America (especially Brazil and Peru), readers are referred to a number of excellent review articles Romania and parts of Australo-Melanesia and the Middle-East have fi (Bangham et al., 2015; Matsuoka and Jeang, 2007; Pique and Jones, been identi ed worldwide (Gessain and Cassar, 2012). Although 2012; Murphy, 2016; Gessain and Cassar, 2012; Kato and Akashi, HTLV-1 was discovered in 1979, there is no recommendation for 2015). systematic screening worldwide. In particular, HTLV-1 prevalence is still poorly understood in several areas of East and North Africa and most parts of Asia, due mainly to a lack of solid data (Murphy, 2016). 2. The HTLV taskforce Furthermore, HTLV-1 and simian T-lymphotropic virus type 1 (STLV-1) can be considered as a single virus infecting and inducing The mission of the Global Virus Network is to strengthen diseases in two different species (Enose-Akahata et al., 2016). Be- medical research and the public health response to viral agents of sides HTLV-1, there is evidence for zoonotic transmission of other human disease and to prepare for new pandemic threats primate T-lymphotropic viruses (Filippone et al., 2015; Richard L. Willems et al. / Antiviral Research 137 (2017) 41e48 43 Fig. 1. The global reach of the HTLV taskforce. Table 1 Members of the GVN taskforce on HTLV-1. Members Home Institution Email address Accolla, Roberto University of Insubria, Varese, Italy [email protected] Bangham, Charles Imperial College, London, UK [email protected] Bazarbachi, Ali American University of Beirut, Beirut, Lebanon [email protected]
Load more

Recommended publications
  • Human T-Lymphotropic Virus Type 1: Technical Report February 2020
    TECHNICAL REPORT HUMAN T-LYMPHOTROPIC VIRUS TYPE 1: TECHNICAL REPORT FEBRUARY 2020 HUMAN T-LYMPHOTROPIC VIRUS TYPE 1: TECHNICAL REPORT FEBRUARY 2020 Human T-lymphotropic virus type 1: technical report ISBN 978-92-4-002022-1 (electronic version) ISBN 978-92-4-002023-8 (print version) © World Health Organization 2021 Some rights reserved. This work is available under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/licenses/by-nc-sa/3.0/igo). Under the terms of this licence, you may copy, redistribute and adapt the work for non-commercial purposes, provided the work is appropriately cited, as indicated below. In any use of this work, there should be no suggestion that WHO endorses any specific organization, products or services. The use of the WHO logo is not permitted. If you adapt the work, then you must license your work under the same or equivalent Creative Commons licence. If you create a translation of this work, you should add the following disclaimer along with the suggested citation: “This translation was not created by the World Health Organization (WHO). WHO is not responsible for the content or accuracy of this translation. The original English edition shall be the binding and authentic edition”. Any mediation relating to disputes arising under the licence shall be conducted in accordance with the mediation rules of the World Intellectual Property Organization (http://www.wipo.int/amc/en/mediation/rules/). Suggested citation. Human T-lymphotropic virus type 1: technical report. Geneva: World Health Organization; 2021.
    [Show full text]
  • Speakers' Biographies 4Th Annual Short Course in Medical Virology Of
    Speakers’ Biographies 4th Annual Short Course in Medical Virology of the GVN Clement A. Adebamowo, BM, ChB, ScD, FWACS, FACS. As a member of the Population Sciences Program of the Cancer Center and a cancer epidemiologist, I conduct research on the epidemiology of cancer. At this time, I am the PI of the NIH funded African Collaborative Center for Microbiome and Genomics Research (ACCME) which is one of the NIH/Wellcome Trust funded Human Heredity and Health in Africa (H3Africa) initiative on genomics research and education in Africa. ACCME’s current project is enrolling 10,000 women in Nigeria and Zambia and following them up every 6 months for research focused on integrative epidemiology of persistent high risk HPV infection, host germline and somatic genomics and epigenomics, and vaginal microenvironment (cytokines and microbiome) and risk of cervical cancer. As part of this project, I established a comprehensive genomics laboratory in Nigeria including facilities for epigenetics and next generation sequencing using Illumina NextSeq500. The genomics lab is linked to an NIH funded biorepository at IHVN. I also direct the Fogarty funded West African Bioethics Training program which has provided medium term training leading to Certificates in Research Ethics for 842 biomedical researchers, Masters’ degree in Bioethics to 34 individuals and Online WAB-CITI Training program to 6115 participants in West Africa. In Baltimore, I am working with colleagues at the University of Maryland Greenebaum Cancer Center and University of Maryland College Park to develop a research program on cancer disparities among Africans in Africa, recent African immigrants to the United States and African Americans in order to better understand the role of genetics, environment cultural and socio- economic factors in cancer prevention, treatment seeking behavior and outcomes.
    [Show full text]
  • GVN Overview | 3 the GENESIS of the GVN the Concept of a Global Virus Network (GVN) Began Back in the 1980’S When Dr
    Overview of the Global Virus Network We represent centers of excellence for research in virology from across the globe. Our work is dedicated to understanding, preventing and eradicating viral disease threats to mankind. Today, we affirm the need for new programs to coordinate, support and promote research that bridges the gap between virus surveillance and public health implementation. We gather in Washington, D.C. to support goals and ideals of the Global Virus Network, a new approach to fostering true collaboration among all regions and all peoples of the world. Seeking to improve the immediate responses to emerging viral threats, train future generations of virologists, and advise governments or non-governmental organizations on viral disease threats and their control, the Global Virus Network fills a critical need in international health for today and into the future. GVN declaration of support was signed March 3, 2011, Washington, D.C. www.gvn.org “The 1918-1919 influenza pandemic killed more people in absolute numbers than any other disease outbreak in history. A contemporary estimate put the death toll at 21 million, a figure that persists in the media today, but understates the real number. Epidemiologists and scientists have revised that figure several times since then. Each and every revision has been upward. Frank Macfarlane Burnet, who won his Nobel prize for immunology but who spent most of his life studying influenza, estimated the death toll as probably 50 million, and possibly as high as 100 million. A 2002 epidemiologic study also estimates the deaths at between 50 and 100 million (Johnson and Mueller, 2002).
    [Show full text]
  • Marburg Virus Outbreak in 1967
    Stigmatized by viral infection Stephan Becker, Philipps-Universität, Marburg, Germany Not many in the general public understand how viruses infect humans or what can be done to prevent their spread. When viral infections spread quickly and result in an outbreak, the psychological effects can surpass the physical as communities deal with treating patients and preventing further occurrences. This can be particularly acute in populations that are unfamiliar with a disease or in situations that lack a carefully planned and engaging communications strategy. Doctor Stephan Becker is a professor at the Institute for Virology, Philipps-Universität in Marburg, Germany and a member of the Global Virus Network’s (GVN) German consortium. He underscores the need for enhanced communication strategies in dealing with viral diseases. As a young virologist, when he had just begun working on his Postdoctoral degree at the Institute of Virology in Marburg, he had the chance to visit two survivors of the Marburg virus outbreak in 1967. “The couple vividly remembered their experiences during this time, when the whole city of Marburg was in the grip of the exotic virus. Although the totality of infected patients was only 32, in the first days of the Marburg outbreak, citizens were very scared, and everybody expected to be the next victim. This had negative consequences for Marburg virus patients who experienced rejections from neighbors and friends. Some nurses, out of fear of becoming infected, refused to enter patients’ rooms, leaving food at the door. Nobody wanted to let their children play with healthy children of Marburg virus patients. Even twenty years later, when sharing their story, the couple was upset and traumatized from the ensuing chaos following the Marburg outbreak.” The Marburg virus was named after the German town where it was first identified in 1967.
    [Show full text]
  • A Global Early Warning System for Pandemics Mobilizing Surveillance for Emerging Pathogens
    A Global Early Warning System for Pandemics Mobilizing Surveillance for Emerging Pathogens ESTHER KROFAH, CARLY GASCA, AND ANNA DEGARMO About the Milken Institute The Milken Institute is a nonprofit, nonpartisan think tank. For the past three decades, the Milken Institute has served as a catalyst for practical, scalable solutions to global challenges by connecting human, financial, and educational resources to those who need them. Guided by a conviction that the best ideas, under-resourced, cannot succeed, we conduct research and analysis and convene top experts, innovators, and influencers from different backgrounds and competing viewpoints. We leverage this expertise and insight to construct programs and policy initiatives. These activities are designed to help people build meaningful lives in which they can experience health and well-being, pursue effective education and gainful employment, and access the resources required to create ever-expanding opportunities for themselves and their broader communities. About FasterCures FasterCures, a center of the Milken Institute, is working to build a system that is effective, efficient, and driven by a clear vision: patient needs above all else. We believe that transformative and lifesaving science should be fully realized and deliver better treatments to the people who need them. ©2021 Milken Institute This work is made available under the terms of the Creative Commons Attribution-NonCommercial- NoDerivs 3.0 Unported License, available at creativecommons.org/licenses/by-nc-nd/3.0/. CONTENTS
    [Show full text]
  • Meeting-Report-The-10Th-International-Global-Virus-Network-Meeting.Pdf
    Antiviral Research 163 (2019) 140–148 Contents lists available at ScienceDirect Antiviral Research journal homepage: www.elsevier.com/locate/antiviral 2018 international meeting of the Global Virus Network T Christian Brechota, Juliet Bryantb, Hubert Endtzc, Robert F. Garryd, Diane E. Griffine, ∗ Sharon R. Lewinf, Natalia Mercera, Albert Osterhausg, Valentina Picotb, Anders Vahlnea,h, , Georges M.G.M. Verjansi,k, Scott Weaverj a The Global Virus Network, Baltimore, MD, USA b Mérieux Foundation, Lyon, France c Mérieux Foundation and the Erasmus University in Rotterdam, the Netherlands d Tulane University, New Orleans, LA, USA e Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA f The Peter Doherty Institute for Infection and Immunity, The University of Melbourne and Royal Melbourne Hospital, Melbourne, and Department of Infectious Diseases, Alfred Health and Monash University, Australia g The University of Veterinary Medicine Hannover, Germany h Division of Clinical Microbiology, Karolinska Institutet, Stockholm, Sweden i Department of Viroscience, Erasmus MC, Rotterdam, the Netherlands j The University of Texas Medical Branch at Galveston, USA k TiHo-RIZ, Hannover, Germany ABSTRACT The Global Virus Network (GVN) was established in 2011 to strengthen research and responses to emerging viral causes of human disease and to prepare against new viral pandemics. There are now 45 GVN Centers of Excellence and 7 Affiliate laboratories in 29 countries. The 10th International GVN meeting was held from November 28–30, 2018 in Veyrier du Lac, France and was co-hosted by the two GVN Centers of Excellence, the Mérieux Foundation and the University of Veterinary Medicine Hannover (TiHo). The theme of this 10th International GVN meeting was “Eradication and control of (re-) emerging viruses”.
    [Show full text]
  • 1520 Cell Dynamics and Immune Response to BLV Infection
    [Frontiers in Bioscience 12, 1520-1531, January 1, 2007] Cell dynamics and immune response to BLV infection: a unifying model 1 1 2 1 1 1 Arnaud Florins , Nicolas Gillet , Becca Asquith , Mathieu Boxus , Catherine Burteau , Jean-Claude Twizere , Patrice Urbain 1, Fabian Vandermeers 1, Christophe Debacq 3, Maria Teresa Sanchez-Alcaraz 4, Isabelle Schwartz-Cornil 5, Pierre Kerkhofs 6, Genèvieve Jean 7, Andre Théwis 7, Jack Hay 8, Franck Mortreux 9, Eric Wattel 9, Michal Reichert 10, 1 1 2 1,11 Arsène Burny , Richard Kettmann , Charles Bangham and Luc Willems 1 Molecular and Cellular biology, FNRS-FUSAG, Gembloux, Belgium, 2 Department of Immunology, Imperial College, London, UK, 3 GlaxoSmithKline Biologicals, Rixensart, Belgium, 4 Department of Medical Genetics and Microbiology, University of Toronto, Toronto, Canada,5 U892 INRA, Jouy-en-Josas, France, 6 Department of Virology, Veterinary and Agrochemical Research Centre, Uccle, Belgium, 7 Zootechny unit, FUSAG, Gembloux, Belgium, 8 Department of Immunology, University of Toronto, Toronto, Canada, 9 Unité d'oncogenèse virale, CNRS UMR5537 Centre Leon Bérard, Lyon, France, 10 Veterinary Research Institute, Pulawy, Poland TABLE OF CONTENTS 1. Abstract 2. Introduction 3. One pathogen in two different hosts developing related diseases 4. Strong but apparently inefficient humoral and cytotoxic immune response 5. Is the virus transcriptionally silent? The caveats of a dogma 6. How does the virus replicate? Viral replication cycle and cellular clonal expansion 7. Does the virus protect from apoptosis? The most straightforward and the alternative interpretations 8. Cell dynamics of pathogenesis in different models 9. Lymphocyte trafficking in lymphoid organs 10. Modulation of viral expression as therapy 11.
    [Show full text]
  • Overview of the Global Virus Network
    Overview of the Global Virus Network We represent centers of excellence for research in medical virology from across the globe. Our work is dedicated to understanding, preventing and eradicating viral disease threats to mankind. Today, we affirm the need for new programs to coordinate, support and promote research that bridges the gap between virus surveillance and public health implementation. We gather in Washington, D.C. to support goals and ideals of the Global Virus Network, a new approach to fostering true collaboration among all regions and all peoples of the world. Seeking to improve the immediate responses to emerging viral threats, train future generations of medical virologists, and advise governments or non-governmental organizations on viral disease threats and their control, the Global Virus Network fills a critical need in international health for today and into the future. GVN declaration of support was signed March 3, 2011, Washington, D.C. www.gvn.org “The 1918-1919 influenza pandemic killed more people in absolute numbers than any other disease outbreak in history. A contemporary estimate put the death toll at 21 million, a figure that persists in the media today, but understates the real number. Epidemiologists and scientists have revised that figure several times since then. Each and every revision has been upward. Frank Macfarlane Burnet, who won his Nobel prize for immunology but who spent most of his life studying influenza, estimated the death toll as probably 50 million, and possibly as high as 100 million. A 2002 epidemiologic study also estimates the deaths at between 50 and 100 million (Johnson and Mueller, 2002).
    [Show full text]
  • A Letter from the GVN Scientific Director and Chair, Scientific Leadership Board
    A Letter from the GVN Scientific Director and Chair, Scientific Leadership Board When the Global Virus Network (GVN) was founded in 2011, our mandate was to safeguard mankind from a potential catastrophic and devastating pandemic virus. To accomplish this, we assembled a network of experts from across the globe to share information, collaborate on research, train virologists, and encourage advocacy among government leaders, the private sector and the scientific community. Since then, we have made great strides in building this worldwide network and educating the next generation of virologists. One important headline is that we have a new leader. In October of 2017, GVN appointed Dr. Christian Bréchot as the next president of GVN. With his extraordinary experience and commitment, Dr. Bréchot is the perfect choice to lead us forward. He has spent his career working on some of the viruses that we are trying to vanquish. Most recently, he has served as president of the Institut Pasteur. Not only does Dr. Bréchot have extraordinary ability in public health and basic science virology, he is also an experienced administrator. His relentless dedication and boundless energy, as well as his breadth of international experience, will help enable GVN to realize its great potential. We are very pleased to have him. As we move forward, the GVN continues to focus on understanding and planning for viral epidemics. We’ve created several task forces to focus on specific viruses, including Zika and HTLV-1, and are closely watching developments related to MERS, Global Virus Network Virion Newsletter 1 Ebola, West Nile virus, polio, measles, and pandemic influenza.
    [Show full text]
  • Leading Virologists Join Together to Tackle Viruses, Leukemia and Neurologic Disorders
    Leading virologists join together to tackle viruses, leukemia and neurologic disorders June 17, 2014: The Global Virus Network (GVN) announced today the launch of a Task Force on HTLV, Human T-Lymphotropic Virus (HTLV), the world's first known human retrovirus and only known leukemia-causing virus. Experts from 11 countries*, led by Dr. Robert Gallo, GVN co- founder and scientific director and director of the Institute of Human Virology (IHV) at the University of Maryland School of Medicine, Dr. Luc Willems (Research Director, National Fund for Scientific Research at University of Liège) and Dr. Hideki Hasegawa (Director, Department of Pathology, National Institute of Infectious Diseases, Japan) are leading the Task Force, which met for the first time last month. "There are no effective vaccines against HTLV, no antiviral drugs to treat infections, and though there are diagnostic tests for the virus none yet can predict which infected person gets disease," said Dr. Gallo who pioneered the field of human retrovirology with his ground- breaking discoveries of HTLV- 1 in 1980 and HTLV-2 in 1982. "This Task Force is critical as the global community works together to address a problem which in many countries is under- recognized and under-appreciated," he continued. More than 20 million people worldwide are infected with the virus, of which up to 10% will develop debilitating and sometimes deadly disease. HTLV causes an adult T-cell leukemia/ lymphoma (ATL), HTLV-associated myelopathy (HAM), spastic paraparesis, and other rare illnesses. Signs and symptoms of HTLV infection include motor and sensory changes in the extremities, inflammation in the spinal cord, a spastic gait in combination with weakness of the lower limbs, cognitive impairment, bladder dysfunction and bladder cancer.
    [Show full text]
  • The Role of Killer Immunoglobulin-Like Receptors In
    The role of killer immunoglobulin-like receptors in HTLV-1 infection A thesis submitted to Imperial College London for the degree of Doctor of Philosophy By Katie R. Twigger Imperial College London 2014 Section of Immunology Department of Medicine Wright-Fleming Institute Imperial College Norfolk Place London W2 1PG Declaration of originality and copyright Copyright The copyright of this thesis rests with the author and is made available under a Creative Commons Attribution-Non Commercial-No Derivatives licence. Researchers are free to copy, distribute or transmit the thesis on the condition that they attribute it, that they do not use it for commercial purposes and that they do not alter, transform or build upon it. For any reuse or distribution, researchers must make clear to others the licence terms of this work. Declaration of originality All work presented in this thesis is the author’s own other than where clearly stated in the ‘Statement of Collaboration’. Signature________________ Date____________________ 2 Summary Human T-lymphotropic virus type 1 (HTLV-1) causes the debilitating neuroinflammatory disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in a minority of infected individuals, while the majority are lifelong asymptomatic carriers (ACs). The effectiveness of the CD8+ T-cell response to HTLV-1 is a major determinant of the HTLV-1 proviral load (PVL) and the associated HAM/TSP risk. Host genotype, particularly of HLA class I, strongly influences CD8+ T-cell effectiveness against HTLV-1. Furthermore, possession of the KIR gene 2DL2 was recently shown to enhance protective and detrimental HLA class I-associated immunity to HTLV-1 and HCV (Seich al Basatena et al., 2011).
    [Show full text]
  • 2016 International Meeting of the Global Virus Network Antiviral
    Antiviral Research 142 (2017) 21e29 Contents lists available at ScienceDirect Antiviral Research journal homepage: www.elsevier.com/locate/antiviral Meeting Report 2016 International meeting of the Global Virus Network Ramesh Akkina a, Heinz Ellerbrok b, William Hall c, Hideki Hasegawa d, * Yasushi Kawaguchi e, Harold Kleanthous f, Edward McSweegan g, , Natalia Mercer g, Victor Romanowski h, Hirofumi Sawa i, Anders Vahlne j a Department of Microbiology, Immunology & Pathology, Colorado State University, Ft. Collins, CO, USA b Centre for Biological Threats and Special Pathogens, Robert Koch-Institute, Berlin, Germany c Department of Medical Microbiology, University College, Dublin, Ireland d National Institute of Infectious Diseases, Tokyo, Japan e Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan f Discovery Research, Sanofi-Pasteur, Boston, MA, USA g Global Virus Network, Baltimore, MD, USA h Institute of Biotechnology & Molecular Biology, Universidad Nacional de La Plata, Argentina i Division of Molecular Pathobiology, Research Center for Zoonosis Control, Hokkaido University, Sapporo, Japan j Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden article info abstract Article history: The Global Virus Network (GVN) was established in 2011 in order to strengthen research and responses Received 24 February 2017 to current viral causes of human disease and to prepare against new viral pandemic threats. There are Accepted 11 March 2017 now 38 GVN Centers of Excellence and 6 Affiliate laboratories in 24 countries. GVN scientists meet Available online 16 March 2017 annually to learn about each other's current research, address collaborative priorities and plan future programs. The 2016 meeting was held from October 23e25 in Hokkaido, Japan, in partnership with the Keywords: Japanese Society for Virology, the National Institute of Infectious Diseases of Japan and the Research Global Virus Network Center for Zoonosis Control of Hokkaido University.
    [Show full text]