Research outline

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  HTLV-1-associated myelopathy (HAM) and adult T-cell leukemia (ATL), both caused by the human retrovirus HTLV-1, frequently occur in Southern Kyushu, an endemic area of the virus in Japan. HAM was discovered at Kagoshima University in 1986. The disease is an inflammatory disease of the spinal cord, and the patients are suffering from gait and urinary disturbance. Various treatments have been tried, but no radical one has been established. Our research division is elucidating the pathogenesis of HAM and developing a new treatment.

Graduate School Graduate School of Medical and Dental Sciences
Course Institute of Research
Field Center for Chronic Viral Diseases
Department Division of Neuroimmunology



TEL.099-275-5941 / FAX.099-275-5942

Research interests

  • Analysis of pathogenesis and development of therapy for HAM
  • Long-term follow up of HAM patients and HTLV-1 carriers
  • lmmune responses in HTLV-1 infection
  • Development of HAM animal model


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Name Ryuji KUBOTA
Specialized field Neuropathology, Neuroimmunology
Research interests ・HTLV-1 and immune responses
・Analysis of pathogenesis and development of therapy for HAM

Researche Repository

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Associate Professor
Name Masakazu TANAKA
Specialized field  Virology,lnfections lmmunology
Research interests Host biological response (HTLV-1 infection and phosphorylation)
・Construction of animal models for HTLV-1 disease
・Development of vaccine to prevent viral infection and onset

Researche Repository

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Specially Appointed Researcher
Specialized field Neuropathology
Research interests ・ Pathogenesis of HAM

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Visiting Researcher
Name Daisuke KODAMA
Specialized field Neurology
Research interests ・Development  of novel therapeutic agents for HAM
・Analysis of glycosylation in HTLV-1 lnfected cells

Research results

  1. Kodama D, Tanaka M, Matsuzaki T, Nozuma S, Matsuura E, Takashima H, Izumo S, Kubota R. Anti-human T-cell leukemia virus type 1 (HTLV-1) antibody assays in cerebrospinal fluid for the diagnosis of HTLV-1-associated myelopathy/tropical spastic paraparesis. J Clin Microbiol. 59(5): e03230-20, 2021.
  2. Kodama D, Tanaka M, Matsuzaki T, Izumo K, Nakano N, Matsuura E, Saito M, Nagai M, Horiuchi M, Utsunomiya A, Takashima H, Kubota R, Izumo S. Inhibition of ABL1 tyrosine kinase reduces HTLV-1 proviral loads in peripheral blood mononuclear cells from patients with HTLV-1-associated myelopathy/tropical spastic paraparesis. PLoS Negl Trop Dis. 2020 14(7): e0008361, 2020.
  3. Matsuura E, Kubota R, Tanaka Y, Takashima H, Izumo S. Visualization of HTLV-1-specific cytotoxic T lymphocytes in the spinal cords of patients with HTLV-1-associated myelopathy/tropical spastic paraparesis. J Neuropath Exp Neurol. 74(1): 2-14, 2015.
  4. Kawabata T, Higashimoto I, Takashima H, Izumo S, Kubota R. Human T-lymphotropic virus type I (HTLV-I)-specific CD8+ cells accumulate in the lungs of patients infected with HTLV-I with pulmonary involvement. J Med Virol. 84(7): 1120-1127, 2012.
  5. Abdullah NH, Abdullah HM, Matsuzaki T, Hayashi D, Tanaka Y, Takashima H, Izumo S, Kubota R. Reduced Tim-3 expression on HTLV-I Tax-specific cytotoxic T lymphocytes in HTLV-I infection. J Infect Dis. 203(7): 948-959, 2011.
  6. Kubota R, Hanada K, Furukawa Y, Arimura K, Osame M, Gojobori T, Izumo S. Genetic stability of human T lymphotropic virus type I despite antiviral pressures by CTLs. J Immunol. 178(9), 5966-5972, 2007.
  7. Kubota R, Furukawa Y, Izumo S, Usuku K, Osame M. Degenerate specificity of HTLV-I-specific CD8+ T cells during viral replication in patients with HTLV-I-associated myelopathy (HAM/TSP). Blood 101(8): 3074-3081, 2003.
  8. Kubota R, Soldan SS, Martin R, Jacobson S. An altered peptide ligand antagonizes antigen-specific T cells of patients with human T lymphotropic virus type I-associated neurological disease. J Immunol. 164: 5192-5198, 2000.
  9. Kubota R, Kawanishi T, Matsubara H, Manns A, Jacobson S. Demonstration of human T lymphotropic virus type I (HTLV-I) tax-specific CD8+ cells directly in peripheral blood of HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients by intracellular cytokine detection. J Immunol. 161: 482-488, 1998.
  10. Greten TF, Slansky JE, Kubota R, Soldan SS, Jaffee EM, Leist TP, Pardoll DM, Jacobson S, Schneck JP. Direct visualization of antigen-specific T lymphocytes: HTLV-I Tax11-19 specific CD8+ T cells are activated in peripheral blood and accumulate in cerebrospinal fluid from HAM/TSP patients. Proc Natl Acad Sci USA. 95: 7568-7573, 1998.
  11. Biddison WE, Kubota R, Kawanishi T, Taub DD, Cruikshank WW, Center DM, Connor EW, Utz U, Jacobson S. Human T cell leukemia virus type I (HTLV-I)-specific CD8+ CTL clones from patients with HTLV-I-associated neurologic disease secrete proinflammatory cytokines, chemokines, and matrix metalloproteinase. J Immunol. 159: 2018-2025, 1997.
  12. Kubota R, Umehara F, Izumo S, Ijichi S, Matsumuro K, Yashiki S, Fujiyoshi T, Sonoda S, Osame M. HTLV-I proviral DNA amount correlates with infiltrating CD4+ lymphocytes in the spinal cord from patients with HTLV-I-associated myelopathy. J Neuroimmunol. 53: 23-29, 1994.
Masakazu TANAKA
  1. Takenouchi N, Tanaka M, Sato T, Yao J, Fujisawa J, Izumo S, Kubota R, Matsuura E. Expression of TSLC1 in patients with HAM/TSP. J NeuroVirology. 26: 404-414, 2020.
  2. Tanaka M, Kawazu Y, Yoshida T, Konishi T, Takenouchi N, Miwa M. Effects of radiation based on whole-body irradiation in HTLV-1-infected mice. J Radiat Res. 60: 710-713, 2019.
  3. Yao J, Tanaka M, Takenouchi N, Ren Y, Lee SI, Fujisawa JI. Induction of APOBEC3B cytidine deaminase in HTLV-1-infected humanized mice. Exp Ther Med. 17: 3701-3708, 2019.
  4. Tanaka M, Tanaka K, Ida C, Oue A, Yamashita S, Yao J, Takenouchi N, Miwa M. Conflicting effects of poly(ADP-ribose)polymerase inhibitor on cell-mediated and virion-mediated HTLV-1 infection. Virus Res. 270: 197653, 2019.
  5. Yamashita S, Tanaka M, Nodono H, Hamada A, Hamada T, Hasegawa M, Nishi Y, Moss J, Miwa M. Human alcohol dehydrogenase 1 is an acceptor protein for polyADP-ribosylation. Biochem Pharmacol. 167: 27-32, 2019.
  6. Yamashita S, Tanaka M, Sato T, Ida C, Ohta N, Hamada T, Uetsuki T, Nishi Y, Moss J, Miwa M. Effect of mild temperature shift on poly(ADP-ribose) and γH2AX levels in cultured cells. Biochem.Biophys.Res.Commun. 476: 594-599, 2016.
  7. Tezuka K, Xun R, Tei M, Ueno T, Tanaka M, Takenouchi N, Fujisawa JI. An animal model of adult T-cell leulemia: humanized mice with HTLV-1-specific immunity. Blood. 123: 346-355, 2014.
  8. Tanaka M, Sun B, Tezuka K, Fujisawa JI, Tanaka Y, Hoshino H, Miwa M. Neuraminidase enhances the initial steps of human T-cell leukemia virus type 1 replication. Microbes Infect. 12: 119-125, 2010.
  9. Tanaka M, Nitta T, Yoshida T, Konishi T, Kawazu Y, Fujisawa JI, Miwa M. Clonal proliferation of HTLV-1-infected cells is associated with spontaneous malignant tumor formation in mice. Int J Oncol. 35: 701-707, 2009.
  10. Nitta T, Tanaka M, Sun B, Sugihara E, Kimura M, Kamada Y, Takahashi H, Hanai S, Jiang S, Fujisawa JI, Miwa M. Reduction of human T-cell leukemia virus type-1 infection in mice lacking nuclear factor-kappaB-inducing kinase. Cancer Sci. 99: 872-878, 2008.
  11.  Tanaka M, Ueno T, Nakahara T, Sasaki K, Ishimoto A, Sakai H. Downregulation of CD4 is required for maintenance of viral infectivity of HIV-1. Virology. 311: 316-325, 2003.
  12. Tanaka M, Sun B, Fang J, Nitta T, Yoshida T, Kohtoh S, Kikukawa H, Hanai S, Uchida K, Miwa M. Human T-cell leukemia virus type 1 (HTLV-1) infection of mice: proliferation of cell clones with integrated HTLV-1 provirus in lymphoid organs. J Virol. 75: 4420-4423, 2001.

Daisuke KODAMA
  1. Kodama D, Saito M, Matsumoto W, Sabouri AH, Izumo S, Arimura K, Usuku K, Bangham CR, Osame M. Longer dinucleotide repeat polymorphism in matrix metalloproteinase-9 (MMP-9) gene promoter which correlates with higher HTLV-I Tax mediated transcriptional activity influences the risk of HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP). J Neuroimmunol. 156(1-2):188-94, 2004.
  2. Umehara F, Yamaguchi N, Kodama D, Takenaga S, Kiwaki T, Sonoda Y, Arimura Y, Yamada H, Arimura K, Osame M. Polyneuropathy with minifascicle formation in a patient with 46XY mixed gonadal dysgenesis. Acta Neuropathol. 98(3):309-12, 1999.
  3. Analysis of HTLV-I proviral load in 202 HAM/TSP patients and 243 asymptomatic HTLV-I carriers: high proviral load strongly predisposes to HAM/TSP.
  4. Nagai M, Usuku K, Matsumoto W, Kodama D, Takenouchi N, Moritoyo T, Hashiguchi S, Ichinose M, Bangham CR, Izumo S, Osame M. J Neurovirol. 4(6):586-93, 1998.

  1. Xing HQ, Zhang Y, Izumo K, Arishima S, Kubota R, Ye X, Xu Q, Mori K, Izumo S.Decrease of aquaporin-4 and excitatory amino acid transporter-2 indicate astrocyte dysfunction for pathogenesis of cortical degeneration in HIV-associated neurocognitive disorders.
    Neuropathology. 2017 Feb;37(1):25-34.
  2. Sakiyama Y, Kanda N, Higuchi Y, Yoshimura M, Wakaguri H, Takata Y, Watanabe O, Yuan J, Tashiro Y, Saigo R, Nozuma S, Yoshimura A, Arishima S, Ikeda K, Shinohara K, Arata H, Michizono K, Higashi K, Hashiguchi A, Okamoto Y, Hirano R, Shiraishi T, Matsuura E, Okubo R, Higuchi I, Goto M, Hirano H, Sano A, Iwasaki T, Matsuda F, Izumo S, Takashima H.New type of encephalomyelitis responsive to trimethoprim/sulfamethoxazole treatment in Japan.Neurol Neuroimmunol Neuroinflamm. 2015 Aug 13;2(5)
  3. Saito M, Tanaka R, Arishima S, Matsuzaki T, Ishihara S, Tokashiki T, Ohya Y, Takashima H, Umehara F, Izumo S, Tanaka Y.Increased expression of OX40 is associated with progressive disease in patients with HTLV-1-associated myelopathy/tropical spastic paraparesis.Retrovirology. 2013 May 7;10:51.

Research Grant List

Project・Event / SpanResearch
 日本医療研究開発機構 新興・再興感染症に対する革新的医薬品等開発推進研究事業          HTLV-1の総合的な感染対策に資する研究
 日本医療研究開発機構 難治性疾患実用化研究事業
 日本医療研究開発機構 難治性疾患実用化研究事業平成26-28年度(分担)
 日本医療研究開発機構 難治性疾患実用化研究事業平成26-28年度(分担)  神経疾患の原因究明および革新的治療法開発に関する研究  
 日本医療研究開発機構  新興・再興感染症に対する革新的医薬品等開発推進研究事業
Masakazu TANAKA
Project・Event / SpanResearch
 厚生労働省科学研究費 新興・再興感染症に対する革新的医薬品等開発推進研究事業 
 厚生労働省科学研究費 新型インフルエンザ等新興・再興感染症研究事業 
 厚生労働省科学研究費 新型インフルエンザ等新興・再興感染症研究事業