2008 Fiscal Year Final Research Report
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
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Project Period (FY) |
2006 – 2008
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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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Research Products
(62 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] 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
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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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[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
Year and Date
20080518-20080524
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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
Year and Date
20060523-20060527
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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
Year and Date
20060000
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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
Year and Date
20060000
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