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]