Identification of novel intrinsic anti-lentiviral defense mechanisms
Project/Area Number |
18689014
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Research Category |
Grant-in-Aid for Young Scientists (A)
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Allocation Type | Single-year Grants |
Research Field |
Virology
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Research Institution | National Institute of Infectious Diseases |
Principal Investigator |
駒野 淳 National Institute of Infectious Diseases (60356251)
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Project Period (FY) |
2006 – 2008
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Project Status |
Completed (Fiscal Year 2008)
|
Budget Amount *help |
¥26,910,000 (Direct Cost: ¥20,700,000、Indirect Cost: ¥6,210,000)
Fiscal Year 2008: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
Fiscal Year 2007: ¥8,710,000 (Direct Cost: ¥6,700,000、Indirect Cost: ¥2,010,000)
Fiscal Year 2006: ¥9,360,000 (Direct Cost: ¥7,200,000、Indirect Cost: ¥2,160,000)
|
Keywords | ウイルス / 生体分子 / 感染症 |
Research Abstract |
我々はHIV-1複製を制御する宿主因子としてHEXIM1,Cyclin K,HSP40B6/DNAJB6,Arp2/3 complex,CD63,Brd4などを同定した。HEXIM1、Cyclin K、Brd4 C末端ドメインはTat/LTR転写を特異的に阻害する事により抗HIV-1複製作用を示し、HSP40B6/DNAJB6は新たなメカニズムでウイルス転写を抑制することによりHIV-1複製を抑止すること、CD63はウイルスレセプターCXCR4の細胞表面発現レベルを低下させることによりHIV-1侵入を阻害すること、Arp2/3複合体がGagと直接相互作用することによりウイルスが細胞に侵入する過程を制御することを証明した。我々は世界でも例をみないユニークなT細胞を使用したHIV-1抵抗性因子をcDNAからスクリーニングする実験系を確立し、これを基幹技術としてさらに数多くのHIV-1複製制御因子を同定し、細胞がもつ内在性抗レトロウイルス因子(intrinsic immunity)に関する研究領域における著しい学術的発展に繋げることに成功した。本研究は霊長類レンチウイルス複製の分子メカニズムを明らかにし、エイズウイルスをはじめとする病原性レトロウイルスの治療法を開発するために大きく貢献し、今後も更なる発展が期待される。
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Report
(4 results)
Research Products
(108 results)
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[Journal Article] Identification of the P-TEFb complex-interacting domain of Brd4 as an inhibitor of HIV-1 replication by functional cDNA library screening in MT-4 cells2008
Author(s)
Urano E, Kariya Y, Futahashi Y, Ichikawa R, Hamatake M, Fukazawa H, Morikawa Y, Yoshida T, Koyanagi Y, Yamamoto N, Komano J.
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Journal Title
FEBS Let. 582(29)
Pages: 4053-8
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[Journal Article] Identification of the P-TEFb complex-interacting domain of Brd4 as an inhibitor of HIV-1 replication by functional cDNA library screening in MT-4 cells.2008
Author(s)
Urano E, Kariya Y, Futahashi Y, Ichikawa R, Hamatake M, Fukazawa H, Morikawa Y, Yoshida T, Koyanagi Y, Yamamoto N, Komano J.
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Journal Title
FEBS Let. Dec 10; 5 82(29)
Pages: 4053-8
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Peer Reviewed
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[Journal Article] SOCSl is aninducible host factor during HN-1 infection and regulates the intracellular trafficking and stability of HN-1 Gag2008
Author(s)
Akihide Ryo, Naomi Tsurutani, Kenji Ohba, Ryuichiro Kimura, Jun Komano, Mayuko Nishi, Hiromi Soedal, Shinichiro Hattori, Kilian Perrem, Mikio Yamamoto, Joh Chiba, Jun-ichi Mimaya, Kazuhisa Yoshimura, Shuzo Matsushita, Mitsuo Honda, Akihiko Yoshimura, Ichiro Aoki, Yuko Morikawa and Naoki Yamamoto
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Journal Title
Proc Natl Acad SciU S A 105(1)
Pages: 297-299
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Peer Reviewed
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[Journal Article] Inhibiting lentiviral replication by HEXIM1, a cellular negative regulator of the CDK9/cyclin T complex2007
Author(s)
Shimizu S, Urano E, Futahashi Y, Miyauchi K, Isogai M, Matsuda Z, Nohtomi K, Onogi T, Takebe Y, Yamamoto N, Komano J.
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Journal Title
Related Report
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[Journal Article] Identification of the suppressive factors for human immunodeficiency virus type-1 replication using the siRNA mini-library directed against host cellular genes2007
Author(s)
Kameoka M, Kitagawa Y, Utachee P, Jinnopat P, Dhepakson P, Isarangkura-na-ayuthaya P, Tokunaga K, Sato H, Komano J, Yamamoto N, Oguchi S, Natori Y, Ikuta K.
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Journal Title
Biochem Biophys Res Commun. 359(3)
Pages: 29-34
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[Journal Article] Identification of the suppressive factors for human immunodeficiencyvirustype-1 replication using the siRNA mini-library directed against host cellular genes2007
Author(s)
Kameoka M, Kitagawa Y, Utachee P, Jinnopat P, Dhepakson P, Isarangkura-na-ayuthaya P, Tokunaga K, Sato H, Komano J, Yamamoto N, Oguchi S, Natori Y, Ikuta K.
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Journal Title
Biochem Biophys Res Commun 359(3)
Pages: 729-734
Related Report
Peer Reviewed
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[Journal Article] Inhibiting lentiviral replication by HEXIM1,a cellular negative regulatoro the CDK9/cyclin T complex2007
Author(s)
Shimizu S, Urano E, Futahashi Y, Miyauchi K, Isogai M, Matsuda Z, Nohtomi K, Onogi T, Takebe Y, Yamamoto N, Komano J.
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Journal Title
AIDS 21(5)
Pages: 575-582
Related Report
Peer Reviewed
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[Journal Article] Inhibiting lentiviral replication by HEX1M1, a cellular inhibitor of cdk9/cyclinT complex.2007
Author(s)
Shimizu S, Urano E, Futahashi Y, Miyjauchi K, Isogai M, Matsuda Z, Nohtomi K, Onogi T, Takebe Y, Yamamoto N, Komano J
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Journal Title
AIDS 21(5)
Pages: 575-582
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[Presentation] Functional substitution of the myristoylation signal of HIV-1 Gag with phospholipase C delta 1 pleckstrin homology domain2008
Author(s)
Toru Aoki, Saki Shimizu, Emiko Urano, Yuko Futahashi, Makiko Hamatake, Kazuo Terashima, Hirokazu Tamamura, Tsutom Murakami, Yuko Morikawa, Naoki Yamamoto, Jun Komano
Organizer
CSH Meeting on Retroviruses
Place of Presentation
Cold Spring Harbor, NY
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[Presentation] Functional substitution of the myristoylation signal of HIV-1 Gag with phospholipase C delta 1 pleckstrin homology domain.2008
Author(s)
Toru Aoki, Saki Shimizu, Emiko Urano, Yuko Futahashi, Makiko Hamatake, Kazuo Terashima, Hirokazu Tamamura, Tsutom Murakami, Yuko Morikawa, Naoki Yamamoto and Jun Komano.
Organizer
CSH Meeting on Retroviruses
Place of Presentation
Cold Spring Harbor, NY USA
Related Report
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[Presentation] T細胞におけるHIV-1抵抗性遺伝子のスクリーニング-Brd4C末端ドメインの同定とその機能解析.2008
Author(s)
駒野淳, 浦野恵美子, 刈屋祐美, 二橋悠子, 市川玲子, 濱武 牧子, 深觸秀輔, 森川裕子, 芳田剛, 小柳義夫, 山本直樹.
Organizer
第56回日本ウイルス学会学術集会
Place of Presentation
岡山
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[Presentation] Rerouting the plasma membrane targeting of HIV-1 and MLV gag by replacing myristoylation signal with membrane proteins2007
Author(s)
Toru Aoki, Saki Shimiz, Urano Emiko, Yuko Futahashi, Makiko Hamatake, Kazuo Terashima, Tsutomu Murakami, Naoki Yamamoto, and Jun Komano
Organizer
CSH Meeting on Retroviruses
Place of Presentation
Cold Spring Harbor, NY, USA
Related Report
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[Presentation] Inhibiting HIV-1 replication by HEXIM1, a cellular inhibitor of cdk9/cyclinT complex (P-TEFb)2006
Author(s)
Saki Shimizu, Emiko Urano, Jun Komano, Yuko Futahashi, Kosuke Miyauchi, Maya Isogai, Zene Matsuda, Kyoko Nohtomi, Kazunari Onogi, Yutaka Takebe, Naoki Yamamoto
Organizer
CSH Meeting on Retroviruses
Place of Presentation
Cold Spring Harbor, NY
Related Report
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[Presentation] Inhibiting HIV-1 replication by HEXIM1, a cellular inhibitor of cdk9/cyclinT complex (P-TEFb)2006
Author(s)
Saki Shimizu, Emiko Urano, Jun Komano, Yuko Futahashi, Kosuke Miyauchi, Maya Isogai, Zene Matsuda, Kyoko Nohtomi, Kazunari Onogi, Yutaka Takebe, Naoki Yamamoto
Organizer
20th IUBMB International Congress of Biochemistry and Molecular Biology and 11th FAOBMB Congress in conjunction with 79th Annual Meeting of the Japanese Biochemical Society and 29th Annual Meeting of the Molecular Biology Society of Japan
Place of Presentation
京都
Related Report
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[Presentation] Inhibiting HIV-1 replication by HEXIM1, a cellular inhibitor of CDK9/Cyclin T complex (P-TEFb)2006
Author(s)
Saki Shimizu, Yutaka Takebem Emiko Urano, Yuko Futahashi, Kosuke Miyauchi, Maya Isogai, Zene Matsuda, Kyoko Nohtomi, Kazunari Onogi, Naoki Yamamoto, Jun Komano
Organizer
7th AIDS Seminar in Kumamoto
Place of Presentation
熊本
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