2001 年度実績報告書

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, 医学系研究科, 教授 (80215417)
研究分担者	増田貴夫東京医科歯科大学, 医歯学総合研究科, 助教授 (80219336) 岡本尚名古屋市立大学, 医学部, 教授 (40146600) 塩田達雄大阪大学, 微生物病研究所, 教授 (00187329) 志田壽利北海道大学, 遺伝子病制御研究所, 教授 (00144395)
キーワード	HIV / エイズ / CD4陽性T細胞 / NF-κB / ケモカインレセプター / レトロウイルス / インテグレーション / 核外移行
研究概要	小柳はウイルス感染個体内でCD4陽性T細胞がアポトーシスに陥るのに関わる細胞性因子であるアポトーシス誘導シグナルとしてFasLでなくTRAILが関与することをSCIDマウスにヒト細胞を移植した感染系を用いて明らかにした。さらに神経組織にウイルスが侵入すると同じTRAILが中枢神経細胞を殺すことを見出した。塩田はウイルスのコレセプターであるCCR5にアジア人特有の遺伝子変異をみつけ、この変異によりこの分子の細胞表面への輸送が低下しHIVに対する感受性が低下することを見つけた。さらにIL-4の遺伝子変異が起こるとエイズ発症が遅延することも見出した。岡本はHIVの転写に必須の細胞性因子としてNF-κBp65のトランス活性化領域に結合してコレプレッサーとして働くAES/TLEとコアクチベーターとして働くFUS/TLSを発見し、ウイルス発現調節機構の新たなメカニズムを明らかにした。増田はHIVインテグレースの細胞核内への移行シグナル部位が従来考えられていたものと異なることを見つけ、この分子移行に関与する細胞性因子の同定を目指している。志田はウイルスRNAの核内から核外へ移行に必須であるウイルス蛋白質Revに結合するCRM1の機能ドメインを明らかにし、Revの多量体化にCRAM1が必要であること、さらにマウス細胞内でも機能を発揮することを見つけ、マウス細胞へのヒトCRAM1遺伝子の導入は意義のあることがわかった。

研究成果

(23件)

すべてその他

すべて文献書誌 (23件)

[文献書誌] Miura Y, Misawa N, Maeda N, Inagaki Y, Tanaka Y, Ito M, Kayagaki N, Yamamoto N, Yagita H, Mizusawa H, Koyanagi Y: "Critical contribution of TNF-related apoptosis-inducing ligand (TRAIL) to apoptosis of human CD4^+ T cells in HIV-1-infected hu-PBL-NOD-SCID mice"Journal of Experimental Medicine. 193. 651-659 (2001)
[文献書誌] Kusagawa, S., Takebe Y, Yang R, Motomura K, Ampofo W, Brandful J, Koyanagi Y, Yamamoto N, Ishikawa K, SataT, Nagai Y, Tatsumi M.: "Isolation and characterization of full-length molecular DNA clones of Ghanaian HIV-1 intersubtype A/G recombinant (CRFO2_AG) which is replication-competent in restricted host-range"AIDS Research and Human Retroviruses. 17. 649-655 (2001)
[文献書誌] Takahashi Y, Tanaka Y, Yamashita A, Koyanagi Y, Nakamura M, Yamamoto N.: "OX40 stimulation by gp34/0X40 ligand enhances productive HIV-1 infection"Journal of Virology. 75. 6748-6757 (2001)
[文献書誌] Takahashi K, Baba S, Koyanagi Y, Yamamoto N, Takaku H, Kawai G: "Two basic regions of NCp7 are sufficient for conformational conversion of HIV-1 dimerization initiation site from kissing-loop dimer to extended-duplex dimer"Journal of Biological Chemistry. 276. 31274-31278 (2001)
[文献書誌] Ishikawa K, Janssens W, Banor JS, Shinno T, Piedate J, Sata T, Ampofo WK, Brandful J, Koyanagi Y, Yamamoto N, Canas-Ferreira WA, Adu-Sarkodie Y, Kurata T.: "Genetic Analysis of HIV Type 2 from Ghana and Guinea-Bissau, West Africa"AIDS Research and Human Retroviruses. 17. 1661-1663 (2001)
[文献書誌] 三浦義治, 小柳義夫: "SCID-huThy/Livマウス"細胞. 32. 44-47 (2000)
[文献書誌] Sakuragi J, Iwamoto A, Shioda T: "Dissociation of genomic dimerization from packaging functions and virion maturation of human immunodeficiecny virus type 1"Journal of Virology. 76. 959-967 (2002)
[文献書誌] Sakuragi J, Shioda T, Panganiban A: "Duplication of the Primary Encapsidation and Dimer Linkage Region of HIV-I RNA Results in the Appearance of Monomeric RNA in Virus Particles"Journal of Virology. 75. 2557-2565 (2001)
[文献書誌] Shioda T.Nakayama E, Tanaka Y, Xin X, Liu H, Kawana-Tachikawa A, Kato A, Sakai Y, Nagai Y, Iwamoto A: "Naturally occurring deletional mutation in the C-terminal cytoplasmic tail of CCR5 affects surface trafficking of CCR5"Journal of Virology. 75. 3462-3468 (2001)
[文献書誌] Nokihara K, Shimizu S, Pipkorn R, Yasuhara T, Shioda T: "Solid-phase synthesis of peptides having difficult sequences : Synthesis of peptides related to HIV-V3 region for immunological studies"Peptide Science. 13-16 (2001)
[文献書誌] Mori K, Yasutomi Y, Ohgimoto S, Nakasone T, Takamura S, Shioda T, Nagai Y: "A quintuple deglycosylation mutant of SIVmac239 in rhesus macaquas. Robust primary replication, tightly contained chronic infection and elicitation of potent immunity against the parental wild type strain"Journal of Virology. 75. 4023-4028 (2001)
[文献書誌] Xin X, Nakamura K, Liu H, Nakayama E, Goto M, Nagai Y, Kitamura Y, Shioda T, Iwamoto A: "Novel polymorphisms in human macrophage inflammatry protein -1 alpha (MIP-1) gene"Genes and Immunity. 2. 156-158 (2001)
[文献書誌] Louisirirotchanakul S, Liu H Roongpisuthipong A, Nakayama E, Takebe Y, Shioda T, Wasi C: "Genetic analysis of HIV-1 discordant couples in Thailand : Association of CCR2 64I homozygosity with HIV-1 negative status"Journal of AIDS.. (印刷中).
[文献書誌] Nakaysmna E, Meyer L, Iwamoto A, Persoz A, Nagai Y, Rouzioux C, Delfraissy J, SEROCO Study Group, Debre P. Mcllroy D, Theodorou I, Shioda T: "Protective effect of IL4 -589T polymorphism on HLV-1 disease progression Relationshin with viral load"Journal of Infectious Diseases. (印刷中).
[文献書誌] Hoshino Y, Nakata K, Hoshino S, Honda Y, Tse D, Shioda T, Rom W, Weiden M: "Maximal HIV-1 replication in alveolar macrophages during tuberculosis requires both lymphocyte contact and cytokines"Journal of Experimental. Medicine. (印刷中).
[文献書誌] Tsurutani N, Kubo M, Maeda Y, Ohasi T, Yamamoto N, Kanagi M, Masuda T: "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] Hakata Y, Yamada M, Mabuchi N, Shida H: "The Carboxy-termina 1 Region of the Human Immunodeficiency Virus-1 Protein Rev has Multiple Roles in Mediating CRM1-related Rev Functions."Journal of Virology. (印刷中).
[文献書誌] Uranishi H, Telsuka T, Yamashita M, Asamitsu K, Shimizu M, Itoh M, Okamoto T: "Involvement of the pro-oncoprotein TLS (Translocated in liposarcoma) in nuclear factor -κB p65-mediated transcription as a coactivator"Journal of Biological Chemistry. 276. 13395-13401 (2001)
[文献書誌] Senoo M, Tsuchiya I, Matsumura Y, Mori T, Saito Y, Kato H, Okamoto T, Habu S: "Thanscriptional dysregulation of the p73L/p63/p51/p40/KET gene in human squamous cell carcinomas : expression of ΔNp73L, a novel dominant-negative isoform, and loss of expression of the potential tumour suppressor p51"British Journal of Cancer. 84. 1235-1241 (2001)
[文献書誌] Ando T, Kawabe T, Ohara H, Ducommun B, Itoh M, Okamoto T: "Involvement of interaction between p21 and PCNA for the maintenance of G2/M arrest after DNA damage"Journal of Biological Chemistry. 276. 42971-42977 (2001)
[文献書誌] Kawabe T, Suganuma M, Ando T, Kimura M, Hori H, Okamoto T: "Cdc25C interacts with PCNA at G2/M transition"Oncogene. (印刷中).
[文献書誌] Sarol LC, Imai K, Asamitsu K, Tetsuka T, Barzaga NG, Okamoto T: "Inhibitory effects of IFN-y on HIV-1 replication in latently infected cells"Biochemical and Biophysical Research. Communications. (印刷中).
[文献書誌] Okamoto T, Asamitsu K, Tetsuka T: "Methods in Enzymology"Academic Press, Inc.. 50 (2001)

2001 年度 実績報告書

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, 医学系研究科, 教授 (80215417)

研究成果

[文献書誌] Takahashi Y, Tanaka Y, Yamashita A, Koyanagi Y, Nakamura M, Yamamoto N.: "OX40 stimulation by gp34/0X40 ligand enhances productive HIV-1 infection"Journal of Virology. 75. 6748-6757 (2001)

[文献書誌] Takahashi K, Baba S, Koyanagi Y, Yamamoto N, Takaku H, Kawai G: "Two basic regions of NCp7 are sufficient for conformational conversion of HIV-1 dimerization initiation site from kissing-loop dimer to extended-duplex dimer"Journal of Biological Chemistry. 276. 31274-31278 (2001)

[文献書誌] 三浦義治, 小柳義夫: "SCID-huThy/Livマウス"細胞. 32. 44-47 (2000)

[文献書誌] Sakuragi J, Iwamoto A, Shioda T: "Dissociation of genomic dimerization from packaging functions and virion maturation of human immunodeficiecny virus type 1"Journal of Virology. 76. 959-967 (2002)

[文献書誌] Sakuragi J, Shioda T, Panganiban A: "Duplication of the Primary Encapsidation and Dimer Linkage Region of HIV-I RNA Results in the Appearance of Monomeric RNA in Virus Particles"Journal of Virology. 75. 2557-2565 (2001)

[文献書誌] Shioda T.Nakayama E, Tanaka Y, Xin X, Liu H, Kawana-Tachikawa A, Kato A, Sakai Y, Nagai Y, Iwamoto A: "Naturally occurring deletional mutation in the C-terminal cytoplasmic tail of CCR5 affects surface trafficking of CCR5"Journal of Virology. 75. 3462-3468 (2001)

[文献書誌] Nokihara K, Shimizu S, Pipkorn R, Yasuhara T, Shioda T: "Solid-phase synthesis of peptides having difficult sequences : Synthesis of peptides related to HIV-V3 region for immunological studies"Peptide Science. 13-16 (2001)

[文献書誌] Xin X, Nakamura K, Liu H, Nakayama E, Goto M, Nagai Y, Kitamura Y, Shioda T, Iwamoto A: "Novel polymorphisms in human macrophage inflammatry protein -1 alpha (MIP-1) gene"Genes and Immunity. 2. 156-158 (2001)

[文献書誌] Louisirirotchanakul S, Liu H Roongpisuthipong A, Nakayama E, Takebe Y, Shioda T, Wasi C: "Genetic analysis of HIV-1 discordant couples in Thailand : Association of CCR2 64I homozygosity with HIV-1 negative status"Journal of AIDS.. (印刷中).

[文献書誌] Hoshino Y, Nakata K, Hoshino S, Honda Y, Tse D, Shioda T, Rom W, Weiden M: "Maximal HIV-1 replication in alveolar macrophages during tuberculosis requires both lymphocyte contact and cytokines"Journal of Experimental. Medicine. (印刷中).

[文献書誌] Tsurutani N, Kubo M, Maeda Y, Ohasi T, Yamamoto N, Kanagi M, Masuda T: "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] Hakata Y, Yamada M, Mabuchi N, Shida H: "The Carboxy-termina 1 Region of the Human Immunodeficiency Virus-1 Protein Rev has Multiple Roles in Mediating CRM1-related Rev Functions."Journal of Virology. (印刷中).

[文献書誌] Uranishi H, Telsuka T, Yamashita M, Asamitsu K, Shimizu M, Itoh M, Okamoto T: "Involvement of the pro-oncoprotein TLS (Translocated in liposarcoma) in nuclear factor -κB p65-mediated transcription as a coactivator"Journal of Biological Chemistry. 276. 13395-13401 (2001)

[文献書誌] Ando T, Kawabe T, Ohara H, Ducommun B, Itoh M, Okamoto T: "Involvement of interaction between p21 and PCNA for the maintenance of G2/M arrest after DNA damage"Journal of Biological Chemistry. 276. 42971-42977 (2001)

[文献書誌] Kawabe T, Suganuma M, Ando T, Kimura M, Hori H, Okamoto T: "Cdc25C interacts with PCNA at G2/M transition"Oncogene. (印刷中).

[文献書誌] Sarol LC, Imai K, Asamitsu K, Tetsuka T, Barzaga NG, Okamoto T: "Inhibitory effects of IFN-y on HIV-1 replication in latently infected cells"Biochemical and Biophysical Research. Communications. (印刷中).

[文献書誌] Okamoto T, Asamitsu K, Tetsuka T: "Methods in Enzymology"Academic Press, Inc.. 50 (2001)

2001 年度実績報告書

小柳義夫東北大学, 医学系研究科, 教授 (80215417)