1990 年度実績報告書

成人T細胞白血病と病因ウイルス

研究課題

研究課題/領域番号	02151007
研究機関	東北大学
研究代表者	菅村和夫東北大学, 医学部, 教授 (20117360)
研究分担者	下遠野邦忠国立がんセンター研究所, 部長 (10000259) 星野洪郎群馬大学, 医学部, 教授 (00107434) 野阪哲哉京都大学, ウイルス研究所, 助手 (30218309) 清木元治金沢大学, がん研究所, 教授 (10154634) 藤沢順一東京大学, 医科学研究所, 助手 (40181341)
キーワード	HTLVーI / ATL / p40^<tax> / 転写活性化因子 / 母子感染 / HTLVーIキャリア
研究概要	HTLVーIによる細胞癌化の分子機構の中で最も重要と考えられるp40^<tax>の転写活性化機構の解析が進展した。p40^<tax>分子とGAL4分子のDNA結合ドメインとを遺伝子上で融合させたところ、この融合分子にp40^<tax>の転写活性化能が証明された。すなわちp40^<tax>はDNA結合分子と直接接触することによって転写活性化を促進するという可能性が示唆された。他方、p40^<tax>の標的塩基配列に結合するCREB様分子が同定され、その中の少なくとも一分子がp40^<tax>と共沈したことからp40^<tax>と複合体を形成している可能性が示された。また細胞質ではp40^<tax>とHSP60の共沈もみられ、p40^<tax>とHSP60の複合体も存在した。HTLVーIのgagーpol間のORFがプロテア-ゼ遺伝子であることが証明され、この領域の転写がリボゾ-ムフレ-ムシフトによることが示された。HTLVーI免疫応答がHLAハプロタイプによって規定され、ATL患者は低応答性であることが明らかとなった。ウサギを用いてHTLVーIの母乳感染が抗HTLVーI陽性ヒト血清IgGの接種によって阻害されることが証明された。

研究成果
(46件)

すべてその他

すべて文献書誌 (46件)

[文献書誌] Ohbo,K.: "Interleukin 6 in cerebrospinal fluid of HTLVーIーassociated myelopathy" Neurology.
[文献書誌] Miura,S.: "Molecular cloning and characterization of a novel glycoprotein,gp34 that is specifically induced by the human Tーcell leukemia virus type I transactivator p40^<tax>" Mol.Cell.Biol.11. 1313-1315 (1991)
[文献書誌] Seiki,M.: "The U5 sequence is a cicーacting repressive element for genomic RNA expression of human T cell leukemia virus type 1" Virology. 176. 81-86 (1990)
[文献書誌] Toyoshima,H.: "Secondary structure of the human Tーcell leukemia virus type 1 rexーresponsive element is essential for rex regulation of RNA processing and transport of unspliced RNAs" J.Virol.64. 2825-2832 (1990)
[文献書誌] Yoshimura,T.: "Multiple cDNA clones encoding nuclear proteins that bind to the taxーdependent enhancer of HTLVー1:all contain a leucine zipper structure and basic amino acid domain" J.Virol.64. 4002-4006 (1990)
[文献書誌] Yoshida,M.: "Control of cellular and HTLVー1 gene expression by regulatory genes (tax and rex)" Human Retroviruses. 1-12 (1990)
[文献書誌] Nagase,T.: "Promoter region of the human CREーBP1 gene encoding the transcriptional regulator binding to the cyclic AMP response element" J.Biol.Chem.265. 17300-17306 (1990)
[文献書誌] Hatanaka,M.: "Discovery of the nucleolar targeting signal" BioEssays. 12. 143-148 (1990)
[文献書誌] Adachi,Y.: "Protein kinase inhibitor Hー7 blocks accumulation of unspliced mRNA of human Tーcell leukemia virus type I (HTLVーI)" Biochem.Biophys.Res.Commun.169. 469-475 (1990)
[文献書誌] Kataoka,R.: "Transmission of HTLVー1 by blood transfusion and its prevention by passive immunization in rabbits" Blood. 76. 1657-1661 (1990)
[文献書誌] Takeuchi,Y.: "Host range mutant of human immunodeficiency virus type 1:Modification of cell tropism by a single point mutation at the neutralization epitope in the env gene" J.Virol.
[文献書誌] Handa,A.: "Inhibition of infection with human immunodeficiency virus type 1 by sulfated gangliosides" B.B.R.C.
[文献書誌] Ohta,M.: "1ck supresses gene expression from various promoters including human Tーcell leukemia virus type 1 promoter" Jpn.J.Cancer Res.81. 440-441 (1990)
[文献書誌] Tanaka,Y.: "Generation and characterization of monoclonal antibodies against multiple epitopes on the Cーterminal half of envelope gp46 of human Tーcell leukemia virus type 1 (HTLVー1)" Int.J.Cancer. 46. 675-681 (1990)
[文献書誌] Hijikata,M.: "Molecular cloning and characterization of a cDNA for a novel phorbolー12ーmyristateー13ーacetateーresponsive gene that is highly expressed in an adult Tーcell leukemia cell line" J.Virol.64. 4632-4639 (1990)
[文献書誌] Nyunoya,H.: "Expression of HTLVー1 envelope protein fused by hydrophobic aminoーterminal peptide of baculoviruse poly edrin in insect cells and its application for serological assays" AIDS Res.Human Retroviruses. 6. 1311-1321 (1990)
[文献書誌] Tanaka,Y.: "Heterogeneity of antigen molecules recognized by antiーtax_1 monoclonal antibody Ltー4 in cell lines bearing human T cell leukemia virus type I and its related retroviruses" Jpn.J.Cancer Res.81. 225-231 (1990)
[文献書誌] Tanaka,Y.: "Recognition of human T cell leukemia virus type I (HTLVーI) gag and pX gene products by MHCーrestricted cytotoxic T lymphocytes induced in rats against syngeneic HTLVーIーinduced cells" J.Immunol.144. 4202-4211 (1990)
[文献書誌] Tanaka,Y.: "Generation and characterization of monoclonal antibodies against multiple epitoeps on the Cーterminal half of envelope gp46 of human Tーcell leukemia virus type I (HTLVーI)" Int.J.Cancer. 46. 675-681 (1990)
[文献書誌] Itoyama,T.: "Cytogentic studies of human Tーcell leukemia virus type I carriers.A family study" Cancer Genet.Cytogenet.48. 157-163 (1990)
[文献書誌] Ikeda,S.: "Detection of preleukemic state of adult Tーcell leukemia (PreーATL) in HTLVーI carriers" Cancer Detection and Prevention. 14. 431-435 (1990)
[文献書誌] Momita,S.: "Survey of antiーhuman Tーcell leukemia virus type I antibody in family members of patients with adult Tーcell leukemia" Jpn.J.Cancer Res.81. 884-889 (1990)
[文献書誌] Isobe,M.: "Rearrangements in the human Tーcell receptor αーchain locus in patients with adult Tーcell leukemia carrying translocations involving chromosome 14q11" Cancer Res.50. 6171-6175 (1990)
[文献書誌] Ogata,M.: "Serum Gc.Hp and γD2HS phenotypes in human Tーlymphotropic leukemia virus type I infection" HUM.HERED.40. 253-256 (1990)
[文献書誌] Sonoda,S.: "Genetic and immunologic determinants of HTLVーIーassociated doseases" In William A.Blattner(ed)“Human Retrovirology HTLV"Raven Press.Ltd.,New York,. 315-326 (1990)
[文献書誌] Nakayama,D.: "Amplification of HTLVー1ーrelated sequences among patients with neurological disorders in highly endemic Nagasaki:Lack of evidence for association of HTLVー1 with multiple sclerosis" Jpn.J.Cancer Res.81. 238-246 (1990)
[文献書誌] Tsuji,Y.: "Prevention of motherーtoーchild transmission of human Tーlymphotropic virus type I" Pediatrics. 86. 11-17 (1990)
[文献書誌] Nomata,K.: "Expression of ras gene family as result of compensatory renal growth in mice" Urol.Res.18. 251-254 (1990)
[文献書誌] Iwahara,Y.,: "Transmission of HTLVーI to rabbits via semen and breast milk from seropositive healthy persons" Int.J.Cancer. 45. 980-983 (1990)
[文献書誌] Kataoka,R.: "Transmission of HTLVーI by blood transfusion and its prevention by passive immunization in rabbits" Blood. 76. 1657-1661 (1990)
[文献書誌] Cockerell,G.L.: "Infection of rabbits with HTLVーI:patterns of antiーviral antibody reactivity and detection of virus by gene amplification" Int.J.Cancer. 45. 127-130 (1990)
[文献書誌] Takehara,N.: "Protection of rabbits against HTLVーI infection by passive immunization" In:Groopman,J.E..,Chen,I.,Essex,M.and Weiss,R.,eds.Human Retroviruses.Alan R.Liss,. 303-312 (1990)
[文献書誌] Ishii,K.: "Isolation of HTLVーI from muscle of a patient with polymyositis" Am.J.Med.
[文献書誌] Seiki,M.: "Intracellular processing and immunogenicity of the envelope proteins of human Tーcell leukemia virus type 1 that are expressed from recombinant vaccinia viruses" Virus Gene. 3. 235-249 (1990)
[文献書誌] Yoshimura,N.K.: "Simian Tーcell leukemia virus type 1 specific killer Tーcells in naturally infected African green monkey carriers" J.Immunol.144. 2173-2178 (1990)
[文献書誌] O'Brien,W.A.: "Virologic aspects of AIDS and the nervous system" Neuropathology of AIDS. 189-207 (1990)
[文献書誌] Chodhury,M.I.H.: "The phorbol ester TPA strongly inhibits HIVー1ーinduced syncytia formation but enhances virus production:Possible involvement of protein kinase C pathway" Virology. 176. 126-132 (1990)
[文献書誌] Pang,S.: "High levels of unintegrated HIVー1 DNA in brain tissue of AIDS dementia patients" Nature. 343. 85-89 (1990)
[文献書誌] Baldwin G.C.: "Human immunodeficiency virus causes mononuclear phagocyte dysfunction" Proc.Natl.Acad.Sci.87. 3933-3937 (1990)
[文献書誌] Chowdhury,M.I.H.: "Mycoplasma and AIDS" Lancer. 336. 247-248 (1990)
[文献書誌] O'Brien,W.A.: "HIVー1 tropism for mononuclear phagocytes can be determined by regions of gp120 outside the CD4ーbinding domain" Nature. 348. 69-73 (1990)
[文献書誌] Takamatsu,K.: "Hepatitis C virus RNA in saliva" Lancet. 336. 1515 (1990)
[文献書誌] Kira,J.: "Increased HTLVーI proviral DNA in HTLVーIーassociated myelopathy" Neurol.
[文献書誌] Matsushita,S.: "Selective killing of HIVーinfected cells by antiーgp120 immunotoxins" Aids Res.Hum.Retrov.6. 193-203 (1990)
[文献書誌] Emini,E.A.: "Antibodyーmediated in vitro neutralization of human immunodeficiency virus type 1 abolishes infectively for chimpanzees" J.Virol.64. 3674-3678 (1990)
[文献書誌] Matsuda,T.: "Generation of neutralizationーresistant HIVーI in vitro due to amino acid interchanges of third hypervariable ENV region" J.Immunol.145. 3240-3246 (1990)

1990 年度 実績報告書

成人T細胞白血病と病因ウイルス

研究代表者

菅村 和夫 東北大学, 医学部, 教授 (20117360)

研究成果

[文献書誌] Ohbo,K.: "Interleukin 6 in cerebrospinal fluid of HTLVーIーassociated myelopathy" Neurology.

[文献書誌] Miura,S.: "Molecular cloning and characterization of a novel glycoprotein,gp34 that is specifically induced by the human Tーcell leukemia virus type I transactivator p40^<tax>" Mol.Cell.Biol.11. 1313-1315 (1991)

[文献書誌] Seiki,M.: "The U5 sequence is a cicーacting repressive element for genomic RNA expression of human T cell leukemia virus type 1" Virology. 176. 81-86 (1990)

[文献書誌] Toyoshima,H.: "Secondary structure of the human Tーcell leukemia virus type 1 rexーresponsive element is essential for rex regulation of RNA processing and transport of unspliced RNAs" J.Virol.64. 2825-2832 (1990)

[文献書誌] Yoshimura,T.: "Multiple cDNA clones encoding nuclear proteins that bind to the taxーdependent enhancer of HTLVー1:all contain a leucine zipper structure and basic amino acid domain" J.Virol.64. 4002-4006 (1990)

[文献書誌] Yoshida,M.: "Control of cellular and HTLVー1 gene expression by regulatory genes (tax and rex)" Human Retroviruses. 1-12 (1990)

[文献書誌] Nagase,T.: "Promoter region of the human CREーBP1 gene encoding the transcriptional regulator binding to the cyclic AMP response element" J.Biol.Chem.265. 17300-17306 (1990)

[文献書誌] Hatanaka,M.: "Discovery of the nucleolar targeting signal" BioEssays. 12. 143-148 (1990)

[文献書誌] Adachi,Y.: "Protein kinase inhibitor Hー7 blocks accumulation of unspliced mRNA of human Tーcell leukemia virus type I (HTLVーI)" Biochem.Biophys.Res.Commun.169. 469-475 (1990)

[文献書誌] Kataoka,R.: "Transmission of HTLVー1 by blood transfusion and its prevention by passive immunization in rabbits" Blood. 76. 1657-1661 (1990)

[文献書誌] Takeuchi,Y.: "Host range mutant of human immunodeficiency virus type 1:Modification of cell tropism by a single point mutation at the neutralization epitope in the env gene" J.Virol.

[文献書誌] Handa,A.: "Inhibition of infection with human immunodeficiency virus type 1 by sulfated gangliosides" B.B.R.C.

[文献書誌] Ohta,M.: "1ck supresses gene expression from various promoters including human Tーcell leukemia virus type 1 promoter" Jpn.J.Cancer Res.81. 440-441 (1990)

[文献書誌] Tanaka,Y.: "Generation and characterization of monoclonal antibodies against multiple epitopes on the Cーterminal half of envelope gp46 of human Tーcell leukemia virus type 1 (HTLVー1)" Int.J.Cancer. 46. 675-681 (1990)

[文献書誌] Hijikata,M.: "Molecular cloning and characterization of a cDNA for a novel phorbolー12ーmyristateー13ーacetateーresponsive gene that is highly expressed in an adult Tーcell leukemia cell line" J.Virol.64. 4632-4639 (1990)

[文献書誌] Nyunoya,H.: "Expression of HTLVー1 envelope protein fused by hydrophobic aminoーterminal peptide of baculoviruse poly edrin in insect cells and its application for serological assays" AIDS Res.Human Retroviruses. 6. 1311-1321 (1990)

[文献書誌] Tanaka,Y.: "Heterogeneity of antigen molecules recognized by antiーtax_1 monoclonal antibody Ltー4 in cell lines bearing human T cell leukemia virus type I and its related retroviruses" Jpn.J.Cancer Res.81. 225-231 (1990)

[文献書誌] Tanaka,Y.: "Recognition of human T cell leukemia virus type I (HTLVーI) gag and pX gene products by MHCーrestricted cytotoxic T lymphocytes induced in rats against syngeneic HTLVーIーinduced cells" J.Immunol.144. 4202-4211 (1990)

[文献書誌] Tanaka,Y.: "Generation and characterization of monoclonal antibodies against multiple epitoeps on the Cーterminal half of envelope gp46 of human Tーcell leukemia virus type I (HTLVーI)" Int.J.Cancer. 46. 675-681 (1990)

[文献書誌] Itoyama,T.: "Cytogentic studies of human Tーcell leukemia virus type I carriers.A family study" Cancer Genet.Cytogenet.48. 157-163 (1990)

[文献書誌] Ikeda,S.: "Detection of preleukemic state of adult Tーcell leukemia (PreーATL) in HTLVーI carriers" Cancer Detection and Prevention. 14. 431-435 (1990)

[文献書誌] Momita,S.: "Survey of antiーhuman Tーcell leukemia virus type I antibody in family members of patients with adult Tーcell leukemia" Jpn.J.Cancer Res.81. 884-889 (1990)

[文献書誌] Isobe,M.: "Rearrangements in the human Tーcell receptor αーchain locus in patients with adult Tーcell leukemia carrying translocations involving chromosome 14q11" Cancer Res.50. 6171-6175 (1990)

[文献書誌] Ogata,M.: "Serum Gc.Hp and γD2HS phenotypes in human Tーlymphotropic leukemia virus type I infection" HUM.HERED.40. 253-256 (1990)

[文献書誌] Sonoda,S.: "Genetic and immunologic determinants of HTLVーIーassociated doseases" In William A.Blattner(ed)“Human Retrovirology HTLV"Raven Press.Ltd.,New York,. 315-326 (1990)

[文献書誌] Nakayama,D.: "Amplification of HTLVー1ーrelated sequences among patients with neurological disorders in highly endemic Nagasaki:Lack of evidence for association of HTLVー1 with multiple sclerosis" Jpn.J.Cancer Res.81. 238-246 (1990)

[文献書誌] Tsuji,Y.: "Prevention of motherーtoーchild transmission of human Tーlymphotropic virus type I" Pediatrics. 86. 11-17 (1990)

[文献書誌] Nomata,K.: "Expression of ras gene family as result of compensatory renal growth in mice" Urol.Res.18. 251-254 (1990)

[文献書誌] Iwahara,Y.,: "Transmission of HTLVーI to rabbits via semen and breast milk from seropositive healthy persons" Int.J.Cancer. 45. 980-983 (1990)

[文献書誌] Kataoka,R.: "Transmission of HTLVーI by blood transfusion and its prevention by passive immunization in rabbits" Blood. 76. 1657-1661 (1990)

[文献書誌] Cockerell,G.L.: "Infection of rabbits with HTLVーI:patterns of antiーviral antibody reactivity and detection of virus by gene amplification" Int.J.Cancer. 45. 127-130 (1990)

[文献書誌] Takehara,N.: "Protection of rabbits against HTLVーI infection by passive immunization" In:Groopman,J.E..,Chen,I.,Essex,M.and Weiss,R.,eds.Human Retroviruses.Alan R.Liss,. 303-312 (1990)

[文献書誌] Ishii,K.: "Isolation of HTLVーI from muscle of a patient with polymyositis" Am.J.Med.

[文献書誌] Seiki,M.: "Intracellular processing and immunogenicity of the envelope proteins of human Tーcell leukemia virus type 1 that are expressed from recombinant vaccinia viruses" Virus Gene. 3. 235-249 (1990)

[文献書誌] Yoshimura,N.K.: "Simian Tーcell leukemia virus type 1 specific killer Tーcells in naturally infected African green monkey carriers" J.Immunol.144. 2173-2178 (1990)

[文献書誌] O'Brien,W.A.: "Virologic aspects of AIDS and the nervous system" Neuropathology of AIDS. 189-207 (1990)

[文献書誌] Chodhury,M.I.H.: "The phorbol ester TPA strongly inhibits HIVー1ーinduced syncytia formation but enhances virus production:Possible involvement of protein kinase C pathway" Virology. 176. 126-132 (1990)

[文献書誌] Pang,S.: "High levels of unintegrated HIVー1 DNA in brain tissue of AIDS dementia patients" Nature. 343. 85-89 (1990)

[文献書誌] Baldwin G.C.: "Human immunodeficiency virus causes mononuclear phagocyte dysfunction" Proc.Natl.Acad.Sci.87. 3933-3937 (1990)

[文献書誌] Chowdhury,M.I.H.: "Mycoplasma and AIDS" Lancer. 336. 247-248 (1990)

[文献書誌] O'Brien,W.A.: "HIVー1 tropism for mononuclear phagocytes can be determined by regions of gp120 outside the CD4ーbinding domain" Nature. 348. 69-73 (1990)

[文献書誌] Takamatsu,K.: "Hepatitis C virus RNA in saliva" Lancet. 336. 1515 (1990)

[文献書誌] Kira,J.: "Increased HTLVーI proviral DNA in HTLVーIーassociated myelopathy" Neurol.

[文献書誌] Matsushita,S.: "Selective killing of HIVーinfected cells by antiーgp120 immunotoxins" Aids Res.Hum.Retrov.6. 193-203 (1990)

[文献書誌] Emini,E.A.: "Antibodyーmediated in vitro neutralization of human immunodeficiency virus type 1 abolishes infectively for chimpanzees" J.Virol.64. 3674-3678 (1990)

[文献書誌] Matsuda,T.: "Generation of neutralizationーresistant HIVーI in vitro due to amino acid interchanges of third hypervariable ENV region" J.Immunol.145. 3240-3246 (1990)

1990 年度実績報告書

菅村和夫東北大学, 医学部, 教授 (20117360)