IRCMS International Research Center for Medical Sciences

Research

Yorifumi Satou
M.D., Ph.D.
Professor

RESEARCH

Analysis of the mechanism of the persistent and latent retroviral infection

There are two retroviruses known to cause human diseases. We are investigating these two retroviruses, HIV and HTLV, in order to elucidate the mechanism of persistent and latent retroviral infection.

 1. HIV (Human Immunodeficiency Virus) infection

There are approximately 34 million people infected with HIV-1 in the world. More than 20,000 people have been positive for HIV-1 in Japan. HIV-1 infection is still spreading in some countries, so HIV infection is a viral infection that requires urgent regulatory and preventive action.

Because of remarkable advance of anti-retroviral therapy, HIV infection has been changed from incurable to controllable viral infection. Yet anti-retroviral therapy can't completely eradicate HIV from infected individuals. Therefore, the patients must continue to take anti-retroviral drugs for a long period. The latent and persistent HIV infection is a cause of such clinical problems.

We are aiming to generate a novel molecular target for the eradication of the latently HIV-1 infected cells via analyzing the mechanism of HIV-1 latency.

2. HTLV (Human T-cell Leukemia Virusinfection

HTLV-1 is a causative agent of adult T-cell leukemia (ATL). There are approximately 20 million people infected with HTLV-1 in the world. Japan is an endemic area and there are about one million people infected with HTLV-1. In particular, there are lots of HTLV-1 carriers in Kyushu and Okinawa area including Kumamoto prefecture. In contrast to HIV-1, HTLV-1 rarely produces the viral particle but maintains latent infection, thereby achieving persistent infection in the infected individuals.

Most of HTLV-1 carriers are asymptomatic and don't cause any disease status, but some carriers develop ATL and/or chronic inflammatory diseases. Our laboratory is trying to develop novel therapeutic strategy or early diagnostic procedure for ATL and HTLV-1 related human diseases.

3. Interaction between retroviral research and human genomic research

Human genomic DNA contains approximately 3.1 billion base pairs as genetic information for our fundamental life activity.

Human genome project had been completed in 2003 and revealed whole DNA sequencing of human genome. However, our knowledge for the mechanism of human diseases still remains elusive. Post genomic research, such as regulatory mechanism of transcription or the role of non-coding transcript would be one of current critical and exciting research area.

HIV-1 and HTLV-1 genome contains just about 9,000 base pairs, but integration of such tiny retroviral genome sometimes causes fatal disease in the infected host. Understanding of how these tiny viruses utilize and disturb huge human genome in order to achieve persistent infection in the host would be a quite unique scientific approach to investigate the regulatory mechanism of human genome.

To address these points, we are going to analyze retroviral integration within human genome by using next generation sequencing techniques, epigenetic regulation of transcription of the integrated provirus, and the effect of three-dimensional spatial localization of the provirus in the nucleus on the regulation of the transcriptional regulation.

We are going to make progress in these researches via collaborating with Prof. CRM Bangham and his colleagues at Imperial College London, UK. Also, all specialized machines required for performing these researches are available as common use machines in the Center for AIDS Research and Institute of Molecular Embryology and Genetics in Kumamoto University.



JOINT RESEARCH

Collaborators in Kumamoto University

  • Prof. Mitsuyoshi Nakao, Department of Medical Cell Biology, Institute of Molecular Embryology and Genetics "Epigenetic analysis of HTLV-1 and HIV-1 provirus"
  • Prof. Shuzo Matsushita, Center for AIDS Research "Analysis of HIV-1 infected patients"
  • Dr. Yoshikazu Uchiyama, Faculty of Life Sciences "Data analysis of next generation sequence"
  • Prof. Tokio Tani, Graduate School of Science and Technology "Analysis of morphological abnormality in Flower cells"
  • Prof. Masao Matsuoka & Dr. Kisato Nosaka, Department of Hematology, Kumamoto University Hospital "Analysis of HTLV-1 infected patients"
  • Prof. Hiroyuki Hata, Faculty of Life Sciences "HTLV-1 study"
  • Dr. Kazuaki Monde, Faculty of Life Sciences "The integration sites study in endogenous retrovirus"

Domestic Collaborators

  • Dr. Atae Utsunomiya, Department of Hematology, Imamura Bun-in Hospital "Analysis of ATL patients"
  • Dr. Masahito Tokunaga, Department of Hematology, Imamura Bun-in Hospital "Analysis of ATL patients"
  • Prof. Hirofumi Akari, Center for Human Evolution Modeling Research, Primate Research Institute, Kyoto University "Dynamics of HIV-1 infection in macaque model"
  • Prof. Yoshio Koyanagi & Dr. Kei Satou, Institute for Virus Research, Kyoto University "HIV-1 study using Humanized mice"
  • Dr. Hodaka Fujii, Research Institute for Microbial Diseases, Osaka University "Analysis of Transcriptional control of HTLV-1 using enChIP"
  • Prof. Jun-ichi Fujisawa & Dr. Takaharu Ueno, Department of Microbiology, Kansai Medical University "HTLV-1 study"
  • Prof. Yoshihisa Yamano, Institute of Medical Science, St. Marianna University Graduate School of Medicine "Analysis of HAM patients"

International Collaborators

  • Prof. Charles RM Bangham, Department of Immunology, Division of Infectious Diseases, Imperial College London, UK "HIV-1 and HTLV-1 integration site analysis by high through-put sequencing"
  • Prof. Graham P Taylor, Section of Infectious Diseases, St Mary's Hospital, Imperial College London, UK "HIV-1/HTLV-1 coinfection study"
  • Prof. Ariberto Fassati, Division of Infection and Immunity, University College London, UK "HIV-1 latent infection study"
  • Prof. Renaud Mahieux, University of Lyon, France "HTLV-1 and HTLV-2 infection study"