The role of HTLV-1 encoded HBZ gene in the pathogenesis

• Project/Area Number: 19390263
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: Kyoto University
• Principal Investigator: MATSUOKA Masao Kyoto University, ウイルス研究所, 教授 (10244138)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥18,850,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥4,350,000); Fiscal Year 2008: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000); Fiscal Year 2007: ¥11,830,000 (Direct Cost: ¥9,100,000、Indirect Cost: ¥2,730,000)
• Keywords: HTLV-1 / ATL / レトロウイルス / HTLV-I

Research Abstract

HTLV-1 bZIP factor (HBZ)遺伝子はHTLV-1プロウイルスマイナス鎖にコードされ、ATL, HTLV-1感染細胞で普遍的に発現している。HBZのプロモーター領域の解析からSp1が転写因子として重要であることを明らかにした。HBZはp65と結合しNF-kB classical pathwayを選択的に抑制する。HBZはp65のDNA結合阻害とp65のE3 ubiquitin ligaseであるPDLIM2発現上昇という異なる機序でclassical pathwayを抑制していた。HBZトランスジェニックマウスでは、高率に皮膚炎・肺胞炎が存在することが明らかとなり、その機序として接着能・遊走能の亢進があることを明らかにした。

Research Products

• [Journal Article] Adult T-cell leukemia/lymphoma; Hematopoietic stem cell transplantation; allogeneic ; reducedintensity transplantation ; anti-thymocyte globulin; graft-versus-ATLL effect (2008)
  • Author(s): Tanosaki R, Uike N, Utsunomiya A, Saburi Y, Masuda M, Tomonaga M, Eto T, Hidaka M, Harada M, Choi I, Yamanaka T, Kannagi M, Matsuoka M and Okamura J
  • Journal Title: Biology of Blood and Marrow Transplantation 14 Pages: 702-708
  • Peer Reviewed
• [Journal Article] A Potential link between alternative splicing of the NBS1 gene and the DNA damage/environmental stress (2008)
  • Author(s): Takai K, Sakamoto S, Sakai T, Yasunaga J-I, Komatsu K and Matsuoka M
  • Journal Title: Radiation Res 170 Pages: 33-40
  • Peer Reviewed
• [Journal Article] Transcriptional control of spliced and unspliced HTLV-1 bZIP factor gene (2008)
  • Author(s): Yoshida M, Satou Y, Yasunaga J-I, Fujisawa JI, Matsuoka M
  • Journal Title: J Virol 82 Pages: 9359-9368
  • Peer Reviewed
• [Journal Article] Roles for microRNAs, miR-93 and miR-130b, and TP53INP1 tumor suppressor in cell growth dysregulation by HTLV-1 (2008)
  • Author(s): Yeung ML, Yasunaga J-I, Bennasser Y, Dusetti N, Harris D, Ahmad N, Matsuoka M, Jeang K-T
  • Journal Title: Cancer Res 68 Pages: 8976-8985
  • Peer Reviewed
• [Journal Article] Broad Anti-Retroviral Activity and Resistance Profile of a Novel Human Immunodeficiency Virus Integrase Inhibitor, Elvitegravir (JTK-303/GS-9137). (2008)
  • Author(s): Shimura K.
  • Journal Title: J Virol. 82 Pages: 764-774
  • Peer Reviewed
• [Journal Article] Adult T-cell leukemia/lymphoma ; Hematopoietic stem cell transplantation ; allogeneic ; reducedintensity transplantation ; anti-thymocyte globulin ; graft versus-ATLL effect. (2008)
  • Author(s): Tanosaki R.
  • Journal Title: Biology of Blood and Marrow Transplantation 14 Pages: 702-708
  • Peer Reviewed
• [Journal Article] A Potential link between alternative splicing of the NBS1 gene and the DNA damage/environmental stress. (2008)
  • Author(s): Takai K.
  • Journal Title: Radiation Res. 170 Pages: 33-40
  • Peer Reviewed
• [Journal Article] Transcriptional control of spliced and unspliced HTLV-1 bZIP factor gene. (2008)
  • Author(s): Yoshida M.
  • Journal Title: J Virol. 82 Pages: 9359-9368
  • Peer Reviewed
• [Journal Article] Roles for microRNAs, miR-93 and miR-130b, and TP53INP1 tumor suppressor in cell growth dysregulation by HTLV-1. (2008)
  • Author(s): Yeung ML.
  • Journal Title: Cancer Res. 68 Pages: 8976-8985
  • Peer Reviewed
• [Journal Article] A Dual-Reporter Phenotypic Assay for Human Immunodeficiency Viruses. (2008)
  • Author(s): Kajiwara K.
  • Journal Title: J Clin Microbiol. 46 Pages: 792-795
  • Peer Reviewed
• [Journal Article] Derse D. Phenotypic and genotypic comparison of human T-cell leukemia virus type 1 reverse transcriptase from infected T-cell lines and patient samples (2007)
  • Author(s): Mitchell MS, Bodine ET, Hill S, Princler G, Lloyd P, Mitsuya H, Matsuoka M
  • Journal Title: J Virol 81 Pages: 4422-4428
  • Peer Reviewed
• [Journal Article] Preferential Selection of HTLV-1 Provirus Lacking the 5'LTR during Oncogenesis (2007)
  • Author(s): Miyazaki M, Yasunaga JI, Taniguchi Y, Tamiya S, Nakahata T and Matsuoka M.
  • Journal Title: J Virol 81 Pages: 5714-5723
  • Peer Reviewed
• [Journal Article] Human T-cell leukemia virus type I induces adult T-cell leukemia: from clinical aspects to molecular mechanisms (2007)
  • Author(s): Yasunaga JI, Matsuoka M.
  • Journal Title: Cancer Control 14 Pages: 133-140
  • Peer Reviewed
• [Journal Article] Development of adult T-cell leukemia in donor-derived human T-cell leukemia virus type I-infected T cells after allogeneic bone marrow transplantation (2007)
  • Author(s): Tamaki H, Taniguchi Y, Kikuchi A, Yamagami T, Soma T and Matsuoka M.
  • Journal Title: Leukemia 21(7) Pages: 1594-1596
  • Peer Reviewed
• [Journal Article] Human T-cell leukemia virus type 1(HTLV-1)infectivity and cellular transformation (2007)
  • Author(s): Matsuoka M and Kuan-The Jeang
  • Journal Title: Nat Rev Can 7 Pages: 270-280
  • Peer Reviewed
• [Journal Article] Implication of the HTLV-I bZIP Factor Gene in the Leukemogenesis of Adult T-Cell Leukemia (2007)
  • Author(s): Satou Y, Matsuoka M
  • Journal Title: International Journal of hematology 86(2) Pages: 107-112
  • NAID: 10019733756
  • Peer Reviewed
• [Journal Article] Leukaemogenic mechanism of human T-cell leukaemia virus type I (2007)
  • Author(s): Yasunaga JI, Matsuoka M
  • Journal Title: Rev Med Virol 17(5) Pages: 301-311
  • Peer Reviewed
• [Journal Article] Cooperation of NF-ΚB2/p100 activation and the PDZ domain binding motif signal in human T-cell leukemia virus type 1 (HTLV) Tax1 but not HTLV-2 Tax2 is crucial for interleukin-2 independent growth transformation of a T cell line (2007)
  • Author(s): Higuchi M, Tsubata C, Kondo R, Yoshida S, Takahashi M, Oie M, Tanaka Y, Mahieux R, Matsuoka M, Fujii M
  • Journal Title: J Virol 81(21) Pages: 119000-11907
  • Peer Reviewed
• [Journal Article] Phenotypic and genotypic comparison of human T-cell leukemia virus type 1 reverse transcriptase from infected T-cell lines and patient samples. (2007)
  • Author(s): Mitchell MS.
  • Journal Title: J Virol. 81 Pages: 4422-4428
  • Peer Reviewed
• [Journal Article] Preferential Selection of HTL V-1 Provirus Lacking the 5' LTR during oncogenesis. (2007)
  • Author(s): Miyazaki M.
  • Journal Title: J Virol. 81 Pages: 5714-5723
  • Peer Reviewed
• [Journal Article] Antiviral Activity against HIV-1, Intracellular Metabolism, and Effects on Human DNA Polymerases of 4'-Ethynyl-2-fluoro-2'-deoxyadenosine. (2007)
  • Author(s): Nakata H.
  • Journal Title: Antimicrob. Agents Chemother. 51 Pages: 2701-2708
  • Peer Reviewed
• [Journal Article] Development of adult T-cell leukemia in donor-derived human T-cell leukemia virus type I-infected T cells after allogeneic bone marrow transplantation. (2007)
  • Author(s): Tamaki H.
  • Journal Title: Leukemia 21 Pages: 1594-1596
  • Peer Reviewed
• [Journal Article] Cooperation of NF-κB2/p100 activation and the PDZ domain binding motif signal in human T-cell leukemia virus type 1 (HTLV) Taxl but not HTLV-2 Tax2 is crucial for interleukin-2 independent growth transformation of a T cell line. (2007)
  • Author(s): Higuchi M
  • Journal Title: J Virol. 81 Pages: 11900-11907
  • Peer Reviewed
• [Journal Article] GANP suppresses DNA recombination, measured by direct-repeat beta-galactosidase gene construct, but does not suppress the type of recombination applying to immunoglobulin genes in mammalian cells. (2007)
  • Author(s): Yoshida M.
  • Journal Title: Genes Cells 12 Pages: 1205-1213
  • Peer Reviewed
• [Journal Article] Heptad repeat-derived peptides block the protease-mediated direct entry from cell surface of SARS coronavirus but not entry via endosomal pathway. (2007)
  • Author(s): Ujike M.
  • Journal Title: J Virol. 82 Pages: 588-592
  • Peer Reviewed
• [Presentation] Molecular pathogenesis and host immune response (2008)
  • Author(s): Matsuoka M.
  • Organizer: IID 2008 Satellite Workshop"Virus-associated Lymphomas"
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2008-05-13
• [Presentation] Molecular pathogenesis and host immune response. (2008)
  • Author(s): Matsuoka M.
  • Organizer: IID 2008 Satellite Workshop "Virus-associated Lymphomas".
  • Place of Presentation: Kyoto, Japan. (京都国際会館)
  • Year and Date: 2008-05-13
• [Presentation] Lentivirus integration and DNA repair. (2008)
  • Author(s): Matsuoka M.
  • Organizer: Ataxia-Telangiectasia Workshop 2008.
  • Place of Presentation: Otsu, Japan. (大津プリンスホテル)
  • Year and Date: 2008-04-22
• [Presentation] ヒトT細胞白血病ウイルスによる病原性発現機構 (2008)
  • Author(s): 松岡雅雄
  • Organizer: 第11回白馬シンポジウム
  • Place of Presentation: 長崎
• [Presentation] ヒトT細胞白血病ウイルスの病原性発現機構 (2008)
  • Author(s): 松岡雅雄
  • Organizer: 第67回日本癌学会総会
  • Place of Presentation: 名古屋
• [Presentation] 造血幹細胞移植療法で治療されたATL患者におけるHTLV-1プロウイルスの解析 (2008)
  • Author(s): 田邉順子、宇都宮興、田野崎隆二、鵜池直邦、佐藤賢文、岡村純、松岡雅雄
  • Organizer: 第67回日本癌学会総会
  • Place of Presentation: 名古屋
• [Presentation] ATL, HTLV-1研究の進歩 (2008)
  • Author(s): 松岡雅雄
  • Organizer: 第70回日本血液学会総会
  • Place of Presentation: 京都
• [Presentation] HTLV-I bZIP factor遺伝子による定型的NF-kB経路の選択的抑制 (2008)
  • Author(s): 趙鉄軍、安永純一朗、中尾光善、藤井雅寛、松岡雅雄
  • Organizer: 第70回日本血液学会総会
  • Place of Presentation: 京都
• [Presentation] HTLV-1 bZIP factor遺伝子プロモーター領域の同定と解析 (2008)
  • Author(s): 吉田美香、佐藤賢文、安永純一朗、藤澤順一、松岡雅雄
  • Organizer: 第1回HTLV-1研究会
  • Place of Presentation: 東京
• [Presentation] HTLV-1 bZIP factor selectively suppresses classical NF-kB pathway (2008)
  • Author(s): 趙鉄軍、安永純一朗、中尾光善、藤井雅寛、松岡雅雄
  • Organizer: 第1回HTLV-1研究会
  • Place of Presentation: 東京
• [Presentation] ヒトT細胞白血病ウイルス1型の病原性発現機構 (2008)
  • Author(s): 松岡雅雄
  • Organizer: 第48回日本リンパ網内系学会総会
  • Place of Presentation: 札幌
• [Presentation] Lentivirus integration and DNA repair (2008)
  • Author(s): Matsuoka M, Sakurai Y, Komatsu K.
  • Organizer: Ataxia-Telangiectasia Workshop 2008
  • Place of Presentation: Otsu, Japan
• [Presentation] HTLV-I bZIP fctor (HBZ)によるT細胞増殖促進の分子機構 (2007)
  • Author(s): 安永純一朗
  • Organizer: 第30回日本分子生物学会年会・第80回日本生化学会大会合同大会
  • Place of Presentation: 横浜(パシフィコ横浜)
  • Year and Date: 2007-12-15
• [Presentation] Molecular mechanism of pathogenesis by human T-cell leukemia virus type I (2007)
  • Author(s): 松岡雅雄
  • Organizer: 第12回慶應医学賞記念シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2007-12-05
• [Presentation] Molecular mechanism of pathogenesis by human T-cell leukemia virus type I (2007)
  • Author(s): 松岡雅雄
  • Organizer: 第12回慶鷹医学賞記念シンポジウム
  • Place of Presentation: 東京(慶応大学)
  • Year and Date: 2007-12-05
• [Presentation] HTLV-I bZIP factor遺伝子のトランスジェニックマウスはHTLV-I関連皮膚疾患、肺疾患に類似した病態を示す (2007)
  • Author(s): 佐藤賢文
  • Organizer: 第37回日本免疫学会総会
  • Place of Presentation: 東京(グランドプリンスホテル新高輪)
  • Year and Date: 2007-11-20
• [Presentation] HTLV-I病原性におけるHBZ遺伝子の機能解析 (2007)
  • Author(s): 佐藤賢文
  • Organizer: 第55回日本ウイルス学会総会
  • Place of Presentation: 札幌(札幌コンベンションセンター)
  • Year and Date: 2007-10-21
• [Presentation] HTLV-1 bZIP factor suppresses canonical pathway of NF-κB by physical interaction with the p65. (2007)
  • Author(s): 趙鉄軍
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 横浜(パシフィコ横浜)
  • Year and Date: 2007-10-03
• [Presentation] HTL V-I bZIP Facotr Gene and Oncogenesis by HTLV-I. (2007)
  • Author(s): Matsuoka M.
  • Organizer: The 13th International Conference on Human Retrovirology.
  • Place of Presentation: Hakone, Japan.(箱根プリンスホテル)
  • Year and Date: 2007-05-22
• [Presentation] HBZ transgenic mice mimic skin and lung diseases associated with HTLV-I. (2007)
  • Author(s): Satou Y.
  • Organizer: The 13th International Conference on Human Retrovirology.
  • Place of Presentation: Hakone, Japan.(箱根プリンスホテル)
  • Year and Date: 2007-05-22
• [Presentation] HTLV-I bZIP fctor(HBZ)によるT細胞増殖促進の分子機構 (2007)
  • Author(s): 安永純一朗
  • Organizer: 第30回日本分子生物学会年会・第80回日本生化学会大会合同大会
  • Place of Presentation: 横浜
• [Presentation] HTLV-I bZIP factor遺伝子のトランスジェニックマウスはHTLV-I関連皮膚疾患、肺疾患に類似した病態を示す (2007)
  • Author(s): 佐藤賢文、片桐晃子、ミヤザトパオラ、木梨達雄、松岡雅雄
  • Organizer: 第37回日本免疫学会総会
  • Place of Presentation: 東京
• [Presentation] HTLV-I 病原性におけるHBZ遺伝子の機能解析 (2007)
  • Author(s): 佐藤賢文、ミヤザトパオラ、松岡雅雄
  • Organizer: 第55回日本ウイルス学会総会
  • Place of Presentation: 札幌
• [Presentation] 欠損型プロウイルスの解析からみた発がんにおけるHTLV-I bZIP factorの重要性 (2007)
  • Author(s): 安永純一朗
  • Organizer: 69回日本血液学会総会・第49回日本臨床血液学会総会
  • Place of Presentation: 横浜
• [Presentation] Leukemogenesis associated wich HTLV-I bZIP factor gene in ATL (2007)
  • Author(s): 松岡雅雄
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 横浜
• [Presentation] HTVL-I bZIP Facotr Gene and Oncogenesis by HTLV-I. (2007)
  • Author(s): Matsuoka M.
  • Organizer: The 13th InternationalCoference on Human Retrovirology.
  • Place of Presentation: Hakone, Japan
• [Presentation] HBZ transgenic mice mimic skin and lung diseases associated with HTLV-I (2007)
  • Author(s): Satou Y, Yasunaga JI, Ohshima k, Miyazato P, Yoshida M, Takai K, Zhao T and Matsuoka M
  • Organizer: The 13th International Conference on Human Retrovirology
  • Place of Presentation: Hakone, Japan
• [Presentation] Characterization of the promoter region for HBZ gene and functional analyses of spliced and unspliced HBZ genes (2007)
  • Author(s): Yoshida M, Matsuoka M.
  • Organizer: The 13th Internationl Conference on Human Retrovirology.
  • Place of Presentation: Hakone, Japan