レトロウイルス(HIV、その他)の増殖・生活環および病原性発現機構の研究

2008 Fiscal Year Annual Research Report

• Project Area: Matrix of Infection Phenomena
• Project/Area Number: 18073008
• Research Institution: Kyoto University
• Principal Investigator: 小柳 義夫 Kyoto University, ウイルス研究所, 教授 (80215417)
• Co-Investigator(Kenkyū-buntansha): 俣野 哲朗 東京大学, 医科学研究所, 教授 (00270653)
• Keywords: HIV / 動物モデル / MHC / 宿主因子 / CXCR4 / 中和抗体 / SIV

Research Abstract

HIV複製と病原性を明らかにするために、ウイルス複製抑制活性のある細胞性因子の作用機序の解明実験とHIVに類似のウイルスであるSIVの感染霊長類モデルを使ってウイルス制御に介在する免疫要因の解明実験をおこなった。まず、HIVの補受容体であるCXCR4の発現を、テトラスパニン分子であるCD63はダウンレギュレーションすること、そして、この活性発現にはその分子の糖鎖修飾が必要であることを見出した。さらに、多くのテトラスパニン分子は、ウイルスエンベロープへ移行し、ウイルス融合を阻害することがわかった。すなわち、テトラスパニンがHIV感染を制御しうることを示した。次に、SIVを使って生体内におけるウイルス複製抑制機序についての解析を行い、感染急性期の中和抗体反応が、高レベルのpolyfunctional CD4陽性T細胞の誘導に結びつき、その結果SIVの複製抑制にいたることを明らかにした。この結果は、感染早期の中和抗体反応が機能的に細胞性免疫を誘導し、その結果ウイルス複製制御に結びつく可能性を示しており、また、polyfunctional CD4陽性T細胞レベルとHIV/SIV複製抑制との相関を初めて示したという点でも重要である。

Research Products

• [Journal Article] Polyfunctional CD4+ T-Cell Induction in Neutralizing Antibody-Triggered Simian Immunodeficiency Virus Control (2009)
  • Author(s): Yamamoto T, Iwamoto N, Yamamoto H, Tsukamoto T, Kuwano T, Takeda A, Kawada M, Tsunetsugu-Yokota Y, Matano T.
  • Journal Title: J. Virol
  • Peer Reviewed
• [Journal Article] A novel CD4-conjugated ultraviolet light-activated photocatalyst inactivates HIV-1 and SIV efficiently (2008)
  • Author(s): Yamaguchi K, Sugiyama T, Kato S, Kondo Y, Ageyama N, Kanekiyo M, Iwata M, Koyanagi Y, Yamamoto N, Honda M.
  • Journal Title: J. Med. Virol. 80 Pages: 1322-1331
  • Peer Reviewed
• [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, and Komano J.
  • Journal Title: FEBS Let 582 Pages: 4053-4058
  • Peer Reviewed
• [Journal Article] A CD63 mutant inhibits T-cell tropic HIV-1 entry by disrupting CXCR4 trafficking to the plasma membrane (2008)
  • Author(s): Yoshida T, Kawano Y, Sato K, Ando Y, Aoki J, Miura Y, Komano J, Tanaka Y, Koyanagi Y.
  • Journal Title: Traffic 9 Pages: 540-558
  • Peer Reviewed
• [Journal Article] Primary target cells of herpes simplex virus type 1 in the hippocampus (2008)
  • Author(s): Ando Y, Kitayama H, Kawaguchi Y, Koyanagi Y.
  • Journal Title: Microbes Infect 10 Pages: 1514-1523
  • Peer Reviewed
• [Journal Article] Anti-HIV adaptive immunity : determinants for viral persistence (2008)
  • Author(s): Yamamoto H, Matano T.
  • Journal Title: Rev Med Virol. 18 Pages: 293-303
  • Peer Reviewed
• [Journal Article] Transmission of simian immunodeficiency virus carrying multiple cytotoxic T-lymphocyte escape mutations with diminished replicative ability can result in AIDS progression in rhesus macaques (2008)
  • Author(s): Seki S, Kawada M, Takeda A, Igarashi H, Sata T, Matano T.
  • Journal Title: J. Virol. 82 Pages: 5093-5098
  • Peer Reviewed
• [Journal Article] Evaluation of the immunogenicity of replication-competent V-knocked-out and replication-defective F-deleted Sendai virus vector-based vaccines in macaques (2008)
  • Author(s): Takeda A, Igarashi H, Kawada M, Tsukamoto T, Yamamoto H, Inoue M, Iida A, Shu T, Hasegawa M, Matano T.
  • Journal Title: Vaccine 26 Pages: 6839-6843
  • Peer Reviewed
• [Journal Article] Potent specific immune responses induced by prime-boost-boost strategies based on DNA, adenovirus, and Sendai virus vectors expressing gag gene of Chinese HIV-1 subtype B (2008)
  • Author(s): Yu S, Feng X, Shu T, Matano T, Hasegawa M, Wang X, Ma H, Li H, Li Z, Zeng Y.
  • Journal Title: Vaccine 26 Pages: 6124-6131
  • Peer Reviewed
• [Journal Article] Gag-specific cytotoxic T-lymphocyte-based control of primary simian immunodeficiency virus replication in a vaccine trial (2008)
  • Author(s): Kawada M, Tsukamoto T, Yamamoto H, Iwamoto N, Kurihara K, Takeda A, Moriya C, Takeuchi H, Akari H, Matano T.
  • Journal Title: J. Virol. 82 Pages: 10199-10206
  • Peer Reviewed
• [Journal Article] Host factors involved in resistance to retroviral infection (2008)
  • Author(s): Takeuchi H, Matano T.
  • Journal Title: Microbiol Immunol 52 Pages: 318-325
  • Peer Reviewed
• [Journal Article] Antigen-specific T-cell induction by vaccination with a recombinant Sendai virus vector even in the presence of vector-specific neutralizing antibodies in rhesus macaques (2008)
  • Author(s): Moriya C, Horiba S, Inoue M, Iida A, Hara H, Shu T, Hasegawa M, Matano T.
  • Journal Title: Biochem Biophys Res Commun. 371 Pages: 850-854
  • Peer Reviewed
• [Journal Article] Determination of a major histocompatibility complex class I restricting simian immunodeficiency virus Gag241-249 epitope (2008)
  • Author(s): Tsukamoto T, Dohki S, Deno T, Kawada M, Takeda A, Yasunami M, Naruse T, Kimura A, Takiguchi M, Matano T.
  • Journal Title: AIDS 22 Pages: 993-994
  • Peer Reviewed
• [Presentation] Induction of functional T-cell responses in neutralizing antibody-triggered SIV control (2008)
  • Author(s): Matano T, Yamamoto T, Iwamoto N, Yamamoto H, Kawada M
  • Organizer: The 26th Annual Symposium on Nonhuman Primate Models for AIDS
  • Place of Presentation: Puerto Rico, Sanjnan
  • Year and Date: 2008-12-12
• [Presentation] Gag特異的CTLクローンのSIV複製抑制能の解析 (2008)
  • Author(s): 石井洋、川田真幹、武内寛明、明里宏文、上野貴将、滝口雅文、俣野哲朗
  • Organizer: 第22回日本エイズ学会
  • Place of Presentation: 大阪市(大阪国際交流センター)
  • Year and Date: 2008-11-28
• [Presentation] レンチウイルスベクターを用いた抗HIV因子のスクリーニングとその解析 (2008)
  • Author(s): 小林朋子、芳田剛、駒野淳、小柳義夫
  • Organizer: 第22回日本エイズ学会
  • Place of Presentation: 大阪市(大阪国際交流センター)
  • Year and Date: 2008-11-27
• [Presentation] CTLエピトープのみ発現する予防エイズワクチンの検討 (2008)
  • Author(s): 塚本徹雄、川田真幹、岩本南、桑野哲矢、井上誠、飯田章博、朱亜峰、長谷川護、俣野哲朗
  • Organizer: 第56回日本ウイルス学会
  • Place of Presentation: 岡山市(岡山コンベンションセンター)
  • Year and Date: 2008-10-28
• [Presentation] サルエイズモデルにおける宿主MHC遺伝子多型の細胞性免疫誘導ワクチン効果への影響の解析 (2008)
  • Author(s): 桑野哲矢、川田真幹、塚本徹雄、岩本南、井上誠、飯田章博、朱亜峰、長谷川護、俣野哲朗
  • Organizer: 第56回日本ウイルス学会
  • Place of Presentation: 岡山市(岡山コンベンションセンター)
  • Year and Date: 2008-10-28
• [Presentation] Small GTPase Rac2によるHIV-1増殖制御 (2008)
  • Author(s): 渡部匡史, 鈴木陽一, 宮澤正顯, 小柳義夫
  • Organizer: 第56回日本ウイルス学会
  • Place of Presentation: 岡山市(岡山コンベンションセンター)
  • Year and Date: 2008-10-27
• [Presentation] Impact of vaccine-induced Gag-specific CTL responses on SIV control (2008)
  • Author(s): 俣野哲朗
  • Organizer: The 9th Kumamoto AIDS Seminar
  • Place of Presentation: 熊本市
  • Year and Date: 2008-09-19
• [Presentation] Characterization of pathogenesis and productive infection of HIV-1 in humanized mice (2008)
  • Author(s): Sato K, Nie C, Misawa N, Tanaka Y, Ito M, Koyanagi Y.
  • Organizer: The 8th Awaji Symposium, Awaji
  • Place of Presentation: 淡路市(淡路夢舞台国際会議場)
  • Year and Date: 2008-09-09
• [Presentation] Induction of CD8 cells with strong anti-SIV efficacy in macaques passively immunized with neutralizing antibody (2008)
  • Author(s): Iwamoto N, Yamamoto H, Tsukamoto T, Kuwano T, Kawada M, Matano T.
  • Organizer: The 8th Awaji International Forum on Infection and Immunity
  • Place of Presentation: 淡路市(淡路夢舞台国際会議場)
  • Year and Date: 2008-09-09
• [Presentation] SIV-specific functional T-cell induction after passive neutralizing antibody immunization postinfection (2008)
  • Author(s): Yamamoto T, Iwamoto N, Yamamoto H, Tsukamoto T, Kuwano T, Takeda A, Kawada M, Tsunetsugu-Yokota Y, Matano T.
  • Organizer: The 8th Awaji International Forum on Infection and Immunity
  • Place of Presentation: 淡路市(淡路夢舞台国際会議場)
  • Year and Date: 2008-09-09
• [Presentation] HIV-1 Vpr in Mitochondria impairs neuronal cell repair (2008)
  • Author(s): Kitayama H, Ando Y, Hoshino S, Ishizaka Y, Koyanagi Y.
  • Organizer: XIV. International Congress of Virology
  • Place of Presentation: Istanbul
  • Year and Date: 2008-08-11
• [Presentation] HIV and AIDS (2008)
  • Author(s): Koyanagi, Y.
  • Organizer: 日中数理生物学コロキュームシンポジウム
  • Place of Presentation: 岡山市(岡山大学)
  • Year and Date: 2008-08-04
• [Presentation] エイズ (2008)
  • Author(s): 俣野哲朗
  • Organizer: 第34回日本医学会シンポジウム
  • Place of Presentation: 東京都
  • Year and Date: 2008-07-17
• [Presentation] A CTL-based AIDS vaccine using a Sendai virus vector (2008)
  • Author(s): 俣野哲朗
  • Organizer: The 7th Japan-China International Conference of Virology
  • Place of Presentation: 東京都
  • Year and Date: 2008-06-02
• [Presentation] Identification of cellular interactors to MoMLV integrase using tandem affinity purification-mass spectrometoy analysis (2008)
  • Author(s): Yamamoto S, Ogawa K, Masuda T, Koyanagi Y, Suzuki Y.
  • Organizer: Retroviruses Meeting, Cold Spring Harbor
  • Place of Presentation: Cold Spring Harbor
  • Year and Date: 2008-05-23
• [Presentation] HIV-1 VPR in mitochondria impairs neuronal progenitor cell differentiation (2008)
  • Author(s): Kitayama H, Miura Y, Ando Y, Hoshino S, Ishizaka Y, Koyanagi Y.
  • Organizer: Retroviruses Meeting, Cold Spring Harbor
  • Place of Presentation: Cold Spring Harbor
  • Year and Date: 2008-05-22
• [Presentation] Tetraspanin on HIV-1 virions modulates its infectivity (2008)
  • Author(s): Sato K, Aoki J, Misawa N, Daikoku E, Sano K, Tanaka Y, Koyanagi Y.
  • Organizer: Retroviruses Meeting, Cold Spring Harbor
  • Place of Presentation: Cold Spring Harbor
  • Year and Date: 2008-05-22
• [Book] Curr. Top. Microbiol. Immunol. (2008)
  • Author(s): Koyanagi Y, Tanaka Y, Ito M, and Yamamoto N
  • Total Pages: 133-148
  • Publisher: Springer