The human T cell leukaemia virus, HTLV-1
The human T-cell leukaemia virus, also known as human T-lymphotropic virus type 1 (HTLV-1) causes two distinct types of disease: an aggressive T-cell leukaemia/lymphoma and a number of chronic inflammatory conditions, notably HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). In 90% of HTLV-1-infected individuals the virus persists indefinitely without causing disease. Neither the pathogenesis of these diseases nor the mechanism of persistent infection of HTLV-1 has been well understood.
We aim to answer three main questions. First, why does a minority of HTLV-I-infected people develop these fatal or disabling diseases, while the great majority remain asymptomatic carriers of the virus? Second, how does HTLV-I spread and persist in the host in the face of a strong cell-mediated immune response? Third, how does the virus regulate the balance between latency and reactivation in vivo?
To answer these questions we have studied host and virus genetic variation, lymphocyte phenotype and function, and the dynamics of HTLV-I replication and the cellular immune response. We have used techniques in molecular genetics, cellular immunology, cell biology, gene expression microarrays, proteomics and mathematical biology. Key contributions include:
- discovery of tissue-resident antigen-specific T lymphocytes (J Exp Med 1998)
- discovery of T-cell fratricide (Immunity 2000)
- discovery of preferential infection of virus-specific T cells (Immunity 2000)
- discovery of the virological synapse (Science 2003)
- protective role of single HLA class 1 genes in viral infection at the population level (PNAS 1999)
- importance of CD8+ T-cell quality in protection against persistent viruses (Science 1996)
- regulation of HTLV-1 clonality and latency in vivo (Blood, PLoS Pathogens, PNAS etc, 2011-2016).
- discovery that HTLV-1 alters the higher-order structure and transcription of host chromatin (PNAS 2016; eLife 2018).
Collaborators
Professor Yorifumi Satou, Kumamoto University, Molecular virology of the human leukaemia virus, HTLV-1, 2016 - 2020
Professor Masao Matsuoka, Kyoto University, Visiting Professorship at Kyoto University. Collaboration on infection with the human leukaemia virus, HTLV-1, 2016 - 2020
Professor Masafumi Takiguchi; Professor Hiroaki Mitsuya, University of Kumamoto
Guest Lectures
Seventh Annual David Derse Memorial Lecture, National Cancer Institute, USA, Frederick, MD, USA, 2018
Invited lecture, 20th Annual International Meeting of the Institute of Human Virology, Baltimore, Md, USA, 2018
Invited lecture, International Symposium of HTLV, Brazil, Belem, Brazil, 2018
Invited lecture, International Retrovirology Association Symposium, Tokyo, Japan, 2018
Invited lecture, International Workshop on ‘Viruses, Genes and Hematological Cancers’, Venice, Italy, 2018
Invited lecture, 19th Annual International Meeting of the Institute of Human Virology, Baltimore, Md, USA, 2017
Invited lecture, 9th International Global Virus Network Meeting (GVN 2017), Melbourne, Australia, 2017
HTLV-1: persistence and pathogenesisInvited keynote lecture, 29th International Workshop on Retroviral Pathogenesis, Prague, Czech Republic, 2017
Plenary Lecture, 29th International Workshop on Retroviral Pathogenesis, Liblice, Czech Republic, 2017
Is HTLV-1 latent in vivo?Invited lecture, Collaborative Research Centre 900 Symposium, Hanover, Germany, 2017
Invited lecture, American Association of Cancer Research, Washington, USA, 2017
How does HTLV-1 cause leukaemia?Invited lecture, American Association of Cancer Research, Washington, USA, 2017
Plenary lecture, 18th International Conference on Human Retrovirology, Tokyo, 2017
Is HTLV-1 really latent in vivo?Invited plenary talk, International Retrovirology Association, Tokyo, Japan, 2017
HTLV-1: THE OTHER HUMAN RETROVIRUS Plenary Lecture., Conference on Retroviruses and Opportunistic Infections (CROI), Seattle, USA, 2017
Plenary Lecture, CROI (Conference on Retroviruses and Opportunistic Infections), Seattle, 2017
How does HTLV-1 cause leukaemia?, International Symposium on Immune Response in Cancer and Infection, Lyon, France, 2017
Invited lecture, International Symposium on Immune Response in Cancer and Infection, Lyon, France, 2017
Plenary Lecture, 28th Annual meeting of the Japanese Society for Neuroimmunology, Nagasaki, Japan, 2016
Ralph Grassmann Memorial Lecture, University of Erlangen, Germany, 2016
Invited Opening Keynote Address, International Retrovirology Association, 16th International Conference on Human Retrovirology, Montreal, June 2013, 2013
Cell to cell spread and CTL response to HTLV-1, Institute of Human Virology, Baltimore, USA, 2004
Immune control, genetics and dynamics of HTLV-1 infection, Japanese Society of Hematology, 2004
Immunogenetics and dynamics of HTLV-1 infection, International Congress of Immunology, Montreal, Canada, 2004
Cellular immune response to HTLV-1, Glaxo Smith Kline, 2004
Dynamics and cell to cell spread of HTLV-1, Univ. of California, San Francisco, 2004
Immune response to HTLV-1, Japanese Association of Immunologists, 2003
Immune response to HTLV-1, University of Kumamoto, Japan, 2003
I do not keep a record of my lectures etc.