2000 年度実績報告書

エイズ制御のための基礎研究柱1.HIVの複製における宿主因子

研究課題

研究課題/領域番号	10180101
研究機関	東北大学
研究代表者	小柳義夫東北大学, 大学院・医学系研究科, 教授 (80215417)
研究分担者	志田壽利北海道大学, 遺伝子病制御研究所, 教授 (00144395) 塩田達雄大阪大学, 微生物病研究所, 教授 (00187329) 岡本尚名古屋市立大学, 医学部, 教授 (40146600) 増田貴夫東京医科歯科大学, 大学院・医歯学総合研究科, 助教授 (80219336)
キーワード	HIV / ケモカインレセプター / ゲノム / TAT / インテグレース / REV / 核内因子 / レトロウイルス
研究概要	1.HIV前期過程に関与する宿主因子ケモカインとコレセプターであるケモカインレセプターにつき、塩田はRantesのレセプターであるCCR5のC末端領域欠損が日本人に多いことを(J.Virol,印刷中)、その他、IL-4やIL-16プロモーターにも変異があり(J.Virol.,2000,Gene ＆ Immunity,2000)、いずれも病状の進行と相関があることを見出し、欧米の結果とは異なる日本人におけるゲノムの変異の存在を証明した。増田はインテグレーションをつかさどるintegraseが逆転写や核移行過程にも関与していることを(J.Virol.,2000)明らかにし、ウイルス蛋白質の機能的多面性を明らかにしている。この機能的多面性は、ゲノムを節約するためのウイルスの戦略であると考えられる。 2.HIV後期過程に関与する宿主因子ウイルス発現過程に関与する宿主因子が明らかになりつつある。岡本は基礎転写因子であるTFIIH複合体の構成成分であるCDK7を抑制するとTat機能が抑制されることを明らかにした(Virology,2000)。志田はウイルスRNAの核外移送をつかさどるRevの多量体化と移送を直接行なうCRM1がどのような相互関係をなしているかを明らかにし、Revと宿主因子との関係がはっきりしてきた。 3.HIV病原性に関与する宿主因子小柳は感染モデル動物であるNOD-SCIDマウスの脾臓においてHIV感染によりTRAIL分子がCD4陽性T細胞へアポトーシスシグナルを送ることを見つけ、生体内における細胞破壊に関与する宿主因子を明らかにした(JEM、印刷中)。

研究成果

(31件)

すべてその他

すべて文献書誌 (31件)

[文献書誌] Takahashi K: "Structural requirement for the two-step dimerization of human immunodeficiency virus type-1 genome"RNA. 6. 96-102 (2000)
[文献書誌] Momoi Y: "Pertusis toxin enhances human immunodefieicncy virus-1 replication"AIDS Research Human Retroviruses. 16. 373-379 (2000)
[文献書誌] Tsunetsugu-Yokota Y: "Transcriptional regulation of HIV-1 LTR during antigen-dependent activation of primary T-cell by dendritic cells"Journal of Leukocyte Biology. 67. 432-440 (2000)
[文献書誌] Takahashi K: "NMR analysis of intra- and inter-molecular stems in the dimerization initiation site of the HIV-1 genome"Journal of Biochemistry. 127. 681-686 (2000)
[文献書誌] Kusagawa,S: "Isolation and characterization of full-length molecular DNA clones of Ghanaian HIV-1 intersubtype A/G recombinant (CRF02_AG) which is replication-competent in restricted host-range"AIDS Research Human Retroviruses,. (印刷中).
[文献書誌] Miura Y: "Critical contribution of TNF-related apotosis-inducing ligand (TRAIL) to apotosis of human CD4^+T cells in HIV-1-infected hu-PBL-NOD-SCID mice"Journal of Experimental Medicine,. (印刷中).
[文献書誌] Okamoto H: "Reciprocal modulation of transcriptional activities between HIV-1 tat and MHC class II transactivator CIITA"Biochemical and Biophysical Research Communication. 279. 494-499 (2000)
[文献書誌] Okamoto H: "Inhibition of the RNA-dependent tansactivation and replication of human immunodeficiency virus type 1 by a fluoroquinoline derivative K-37"Virology. 272. 402-408 (2000)
[文献書誌] Kanazawa S: "Tat competes with CIITA for the binding to P-TEFb and blocks the expression of MHC class II genes in HIV infection"Immunity. 12. 61-70 (2000)
[文献書誌] Okamoto H: "HIV-1 replication is inhibited by a pseudo-substrate peptide that blocks Tat transactivation"Virology. 270. 337-344 (2000)
[文献書誌] Tetsuka T: "Inhibition of nuclear facter-?B-mediated transcription by association with the amino-terminal rnhancer of split (AES), a groucho-related protein lacking WD40 repeats"Journal of Biological Chemistry. 275. 4383-4390 (2000)
[文献書誌] Kameoka M: "Evidence for Regulation of NF-?B by Poly (ADP-ribose) Polymerase"Biochemical Journal. 346. 641-649 (2000)
[文献書誌] Kajino S: "Evidence that de novo protein synthesis is dispensable for anti-apoptotic effects of NF-?B"Oncogene. 19. 2233-2239 (2000)
[文献書誌] Nagaya T: "A potential role of activated NF-?B in the pathogenesis of euthyroid sick syndrome"Journal of Clinical Investigation. 106. 393-402 (2000)
[文献書誌] Suzuki M: "The role of p38 mitogen-activated protein kinase in IL-6 and IL-8 production from the TNF-a or IL-1β stimulated rheumatoid synovial fibroblasts"FEBS Letters. 465. 23-27 (2000)
[文献書誌] Mori T: "Aberrant overxpressin of 53BP2 mRNA in lung cancer cell lines"FEBS Letters. 465. 124-128 (2000)
[文献書誌] UranishI H: "Involvement of TLS/FUS in the NF-?B p65-mediated transactivation"Journal of Biological Chemistry,. (印刷中).
[文献書誌] Senoo M: "Transcriptional dysregulation of the p73L/p63/p51/p40/KET gene, which encodes both the tumor suppressor protein p51 and its dominant-negative form p73L, in human skin cancers"British Journal of Cancer,. (印刷中).
[文献書誌] Nakayama E E: "A new polymorphism in promoter region of human interleukin 16 gene"Genes and Immunity. 1. 293-294 (2000)
[文献書誌] Nakayama E E: "Polymorphism in IL-4 promoter affects acquisition of human immunodeficiency virus type 1 syncytium inducing phenotype"Journal of Virology. 74. 5452-5459 (2000)
[文献書誌] Ohnishi Y: "Crystal structure of recombinant native SDF-1a with additional mutagenesis studies. An attempt for more comprehensive interpretation of accumulated structure-activity relationship data"Journal of Interferon and Cytokine Research. 20. 691-700 (2000)
[文献書誌] Watanabe Y: "Antibodies to molluscum contagiosum virus in the general population and susceptible patients"Archives of Dermatology. 136. 1518-1522 (2000)
[文献書誌] Sakuragi J-I: "Duplication of the primary encapsidation and dimer linkage region of HIV-1 RNA results in the appearance of monomeric RNA in virions"Journal of Virology、. (印刷中).
[文献書誌] Shioda,T: "Naturally occurring deletional mutation in the C-terminal cytoplasmic tail of CCR5 affects surface trafficking of CCR5"Journal of Virology、. (印刷中).
[文献書誌] Nokihara K: "Solid-phase synthesis of peptides having difficult sequences : Synthesis of peptides related to the HIV-V3 region for immunological studies"Peptide Science、. (印刷中).
[文献書誌] Mori K: "A quintuple deglycosylation mutant of SIVmac239 in rhesus macaques. Robust primary replication, tightly contained chronic infection and elicitation of potent immunity against the parental wild type strain"Journal of Virology、. (印刷中).
[文献書誌] Xiao Y: "Dox-dependent SIVmac with tetracycline inducible promoter in the U3 promoter region"Virology. 269. 268-275 (2000)
[文献書誌] Huemer H P: "Induction of recombinant gene expression in stablely transfected cell lines using attenuated vaccinia virus MVA expressing T7 RNA polymerase with a nuclear localization signal"Journal Virological Method. 85. 1-10 (2000)
[文献書誌] Shida H: "Regulation of mRNA transport of human retroviruses"Recent Research developments in Virology. 2. 51-65 (2000)
[文献書誌] Tsurutani N: "Identification of Critical Amino Acid Residues in HIV-1 IN Required for Efficient Proviral DNA Formation at Steps Prior to Integration in Dividing and Non-dividing Cells"Journal of Virology. 74. 4795-4806 (2000)
[文献書誌] 岡本完,岡本尚(斉藤英彦,吉田純編): "AIDSの遺伝子治療「遺伝子医療」"財団法人名古屋大学出版会. 180 (2000)

2000 年度 実績報告書

エイズ制御のための基礎研究柱1.HIVの複製における宿主因子

研究代表者

小柳 義夫 東北大学, 大学院・医学系研究科, 教授 (80215417)

研究成果

[文献書誌] Takahashi K: "Structural requirement for the two-step dimerization of human immunodeficiency virus type-1 genome"RNA. 6. 96-102 (2000)

[文献書誌] Momoi Y: "Pertusis toxin enhances human immunodefieicncy virus-1 replication"AIDS Research Human Retroviruses. 16. 373-379 (2000)

[文献書誌] Tsunetsugu-Yokota Y: "Transcriptional regulation of HIV-1 LTR during antigen-dependent activation of primary T-cell by dendritic cells"Journal of Leukocyte Biology. 67. 432-440 (2000)

[文献書誌] Takahashi K: "NMR analysis of intra- and inter-molecular stems in the dimerization initiation site of the HIV-1 genome"Journal of Biochemistry. 127. 681-686 (2000)

[文献書誌] Kusagawa,S: "Isolation and characterization of full-length molecular DNA clones of Ghanaian HIV-1 intersubtype A/G recombinant (CRF02_AG) which is replication-competent in restricted host-range"AIDS Research Human Retroviruses,. (印刷中).

[文献書誌] Miura Y: "Critical contribution of TNF-related apotosis-inducing ligand (TRAIL) to apotosis of human CD4^+T cells in HIV-1-infected hu-PBL-NOD-SCID mice"Journal of Experimental Medicine,. (印刷中).

[文献書誌] Okamoto H: "Reciprocal modulation of transcriptional activities between HIV-1 tat and MHC class II transactivator CIITA"Biochemical and Biophysical Research Communication. 279. 494-499 (2000)

[文献書誌] Okamoto H: "Inhibition of the RNA-dependent tansactivation and replication of human immunodeficiency virus type 1 by a fluoroquinoline derivative K-37"Virology. 272. 402-408 (2000)

[文献書誌] Kanazawa S: "Tat competes with CIITA for the binding to P-TEFb and blocks the expression of MHC class II genes in HIV infection"Immunity. 12. 61-70 (2000)

[文献書誌] Okamoto H: "HIV-1 replication is inhibited by a pseudo-substrate peptide that blocks Tat transactivation"Virology. 270. 337-344 (2000)

[文献書誌] Tetsuka T: "Inhibition of nuclear facter-?B-mediated transcription by association with the amino-terminal rnhancer of split (AES), a groucho-related protein lacking WD40 repeats"Journal of Biological Chemistry. 275. 4383-4390 (2000)

[文献書誌] Kameoka M: "Evidence for Regulation of NF-?B by Poly (ADP-ribose) Polymerase"Biochemical Journal. 346. 641-649 (2000)

[文献書誌] Kajino S: "Evidence that de novo protein synthesis is dispensable for anti-apoptotic effects of NF-?B"Oncogene. 19. 2233-2239 (2000)

[文献書誌] Nagaya T: "A potential role of activated NF-?B in the pathogenesis of euthyroid sick syndrome"Journal of Clinical Investigation. 106. 393-402 (2000)

[文献書誌] Suzuki M: "The role of p38 mitogen-activated protein kinase in IL-6 and IL-8 production from the TNF-a or IL-1β stimulated rheumatoid synovial fibroblasts"FEBS Letters. 465. 23-27 (2000)

[文献書誌] Mori T: "Aberrant overxpressin of 53BP2 mRNA in lung cancer cell lines"FEBS Letters. 465. 124-128 (2000)

[文献書誌] UranishI H: "Involvement of TLS/FUS in the NF-?B p65-mediated transactivation"Journal of Biological Chemistry,. (印刷中).

[文献書誌] Senoo M: "Transcriptional dysregulation of the p73L/p63/p51/p40/KET gene, which encodes both the tumor suppressor protein p51 and its dominant-negative form p73L, in human skin cancers"British Journal of Cancer,. (印刷中).

[文献書誌] Nakayama E E: "A new polymorphism in promoter region of human interleukin 16 gene"Genes and Immunity. 1. 293-294 (2000)

[文献書誌] Nakayama E E: "Polymorphism in IL-4 promoter affects acquisition of human immunodeficiency virus type 1 syncytium inducing phenotype"Journal of Virology. 74. 5452-5459 (2000)

[文献書誌] Ohnishi Y: "Crystal structure of recombinant native SDF-1a with additional mutagenesis studies. An attempt for more comprehensive interpretation of accumulated structure-activity relationship data"Journal of Interferon and Cytokine Research. 20. 691-700 (2000)

[文献書誌] Watanabe Y: "Antibodies to molluscum contagiosum virus in the general population and susceptible patients"Archives of Dermatology. 136. 1518-1522 (2000)

[文献書誌] Sakuragi J-I: "Duplication of the primary encapsidation and dimer linkage region of HIV-1 RNA results in the appearance of monomeric RNA in virions"Journal of Virology、. (印刷中).

[文献書誌] Shioda,T: "Naturally occurring deletional mutation in the C-terminal cytoplasmic tail of CCR5 affects surface trafficking of CCR5"Journal of Virology、. (印刷中).

[文献書誌] Nokihara K: "Solid-phase synthesis of peptides having difficult sequences : Synthesis of peptides related to the HIV-V3 region for immunological studies"Peptide Science、. (印刷中).

[文献書誌] Mori K: "A quintuple deglycosylation mutant of SIVmac239 in rhesus macaques. Robust primary replication, tightly contained chronic infection and elicitation of potent immunity against the parental wild type strain"Journal of Virology、. (印刷中).

[文献書誌] Xiao Y: "Dox-dependent SIVmac with tetracycline inducible promoter in the U3 promoter region"Virology. 269. 268-275 (2000)

[文献書誌] Huemer H P: "Induction of recombinant gene expression in stablely transfected cell lines using attenuated vaccinia virus MVA expressing T7 RNA polymerase with a nuclear localization signal"Journal Virological Method. 85. 1-10 (2000)

[文献書誌] Shida H: "Regulation of mRNA transport of human retroviruses"Recent Research developments in Virology. 2. 51-65 (2000)

[文献書誌] Tsurutani N: "Identification of Critical Amino Acid Residues in HIV-1 IN Required for Efficient Proviral DNA Formation at Steps Prior to Integration in Dividing and Non-dividing Cells"Journal of Virology. 74. 4795-4806 (2000)

[文献書誌] 岡本完,岡本尚(斉藤英彦,吉田純 編): "AIDSの遺伝子治療「遺伝子医療」"財団法人名古屋大学出版会. 180 (2000)

2000 年度実績報告書

小柳義夫東北大学, 大学院・医学系研究科, 教授 (80215417)

[文献書誌] 岡本完,岡本尚(斉藤英彦,吉田純編): "AIDSの遺伝子治療「遺伝子医療」"財団法人名古屋大学出版会. 180 (2000)