新規ウィルスレセプター:抑制化PILRを介する新たなウィルス感染機構の解明

• Project/Area Number: 19041040
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Osaka University
• Principal Investigator: 荒瀬 尚 Osaka University, 微生物病研究所, 教授 (10261900)
• Co-Investigator(Kenkyū-buntansha): 末永 忠広 大阪大学, 微生物病研究所, 助教 (20396675) ; 上掘 淳二 (上堀 淳二) 大阪大学, 微生物病研究所, 助教 (20432429) ; 佐藤 毅史 大阪大学, 微生物病研究所, 助教 (10432428)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥15,200,000 (Direct Cost: ¥15,200,000); Fiscal Year 2008: ¥7,700,000 (Direct Cost: ¥7,700,000); Fiscal Year 2007: ¥7,500,000 (Direct Cost: ¥7,500,000)
• Keywords: 単純ペルペスウィルスI型 / PILR / ウィルス感染 / ウィルスエントリー / 抑制化レセプター / ヘルペスウィルス / 単純ヘルペスウィルス / ペア型レセプター / NK細胞 / 免疫逃避 / ウィルスレセプター / Glycoprotein B

Research Abstract

私どもは、免疫細胞の発現するペア型レセプターが病原体の認識と密接な関連があるではないかと新たな仮説を立てて研究した結果、その一つである抑制化レセプターPILRが、単純ペルペスウィルスI型のGlycoprotein Bと会合し、単純ペルペスウィルスI型のエントリーレセプターであることを発見した。本研究では、PILRを介した単純ペルペスウィルスI型の感染機構の解明、およびその阻害法の研究を行った。その結果、PILRはGlycoprotein B上の特定の糖鎖を認識し、Glycoprotein B上の特定の糖鎖がHSVの感染に重要であることが明らかになった。さらに、PILRによるgBの認識機構を解析することにより、PILRのGlycoprotein Bの認識にはペプチド構造と糖鎖構造の双方が必要であることが判明した。また、PILRとの相互作用に必須である糖鎖構造を持たない単純ペルペスウィルスI型はPILR発現細胞ばかりでなくVero細胞等のPILR陰性細胞にも感染しないことから、Vero細胞等にはPILRと同様な特異性をもったPILR以外のウィルスレセプターが存在する可能性が明らかになった。また、他のウィルスについてPILRの機能を調べると単純ヘルペスウィルスばかりでなくブタウィルスであるPseudorabies virusのGlycoprotein BもPILRと会合し、PILRを介して感染することが明らかになった。

Research Products

• [Journal Article] Differential effects on cell fusion activity of mutations in herpes simplex virus 1 glycoprotein B (gB) dependent on whether a gD receptor or a gB receptor is overexpressed. (2009)
  • Author(s): Fan, Q., Lin, E., Satoh, T., Arase, H., Spear, P.G.
  • Journal Title: Virol. 83 Pages: 7384-7390
  • Peer Reviewed
• [Journal Article] Herpes simplex virus 1 protein kinase Us3 phosphorylates viral envelope glycoprotein B and regulates its expression on the cell surface. (2009)
  • Author(s): Kato, A., Arii, J., Shiratori, I., Akashi, H., Arase, H., Kawaguchi, Y.
  • Journal Title: J.Virol. 83 Pages: 250-261
  • Peer Reviewed
• [Journal Article] Ly49H signaling through DAP10 is essential for optimal natural killer cell responses to mouse cytomegalovirus infection. (2009)
  • Author(s): Orr, M.T., Sun, J.C., Hesslein, D.G., Arase, H., Phillips, J.H., Takai, T., Lanier, L.L.
  • Journal Title: J.Exp.Med. 206 Pages: 807-817
  • Peer Reviewed
• [Journal Article] Ly49Q ligand expressed by activated B cells induces plasmacytoid DC maturation (2009)
  • Author(s): Toma-Hirano, M., Namiki, S., Shibata, Y., Ishida, K., Arase, H., Miyatake, S., Arai, K., Kamogawa-Schifter, Y.
  • Journal Title: Eur.J.Immunol. 39 Pages: 1344-1352
  • Peer Reviewed
• [Journal Article] Modulation of dendritic cell differentiation by HLA-G and ILT4 requires the IL-6-STAT3 signaling pathway. (2008)
  • Author(s): Liang, S., Ristich, V., Arase, H., Dausset, J., Carosella, E.D., Horuzsko, A.
  • Journal Title: Proc.Natl.Acad.Sci.USA. 105 Pages: 8357-8362
  • Peer Reviewed
• [Journal Article] Bimodal regulation of T cell-mediated immune responses by TIM-4. (2008)
  • Author(s): Mizui, M., Shikina, T., Arase, H., Suzuki, K., Yasui, T., Rennert, P.D., Kumanogoh, A., Kikutani, H.
  • Journal Title: Int.Immunol. 20 Pages: 695-708
  • NAID: 10021241281
  • Peer Reviewed
• [Journal Article] PILRα is a herpes simplex virus-1 entry co-receptor that associates with glycoprotein B. (2008)
  • Author(s): Satoh, T., Arii, J., Suenaga, T., Wang, J., Kogure, A., Uehori, J., Arase, N., Shiratori, I., Tanaka, S., Kawaguchi, Y., Spear, P.G., Lanier, L.L., Arase, H.
  • Journal Title: Cell 132 Pages: 935-944
  • Peer Reviewed
• [Journal Article] Biophysical characterization of O-glycosylated CD99 recognition by paired Ig-like type 2 receptors (PILR) (2008)
  • Author(s): Tabata, S., Kuroki, K., Wang, J., Kajikawa, M., Shiratori, I., Kohda, D., Arase, H., Maenaka, K.
  • Journal Title: J.Biol.Chem. 283 Pages: 8893-8901
  • Peer Reviewed
• [Journal Article] An essential role of sialylated O-linked sugar chains in the recognition of mouse CD99 by paired immunoglobulin-like type 2 receptor (PILR). (2008)
  • Author(s): Wang, J., Shiratori, I., Satoh, T., Lanier, L.L., Arase, H.
  • Journal Title: J.Immunol. 180 Pages: 1686-1693
  • Peer Reviewed
• [Journal Article] xpression, crystallization and preliminary x-ray diffraction analysis of human paired Ig-like type 2 receptor α(PILRα). (2008)
  • Author(s): Tabata, S., Kuroki, K., Maita, N., Wang, J., Shiratori, I., Arase, H., Kohda, D., Maenaka, K.
  • Journal Title: J.Immunol. 64 Pages: 44-46
  • Peer Reviewed
• [Journal Article] PILRα is a herpes simplex virus-1 entry co-receptor that associates with glycoprotein B (2008)
  • Author(s): Satoh, T., Arii, J., Suenaga, T., Wang, J., Kogure, A., Uehori, J., Arase, N., Shiratori, I., Tanaka, S., Kawaguchi, Y., Spear, P. G., Lanier, L. L. and Arase, H.
  • Journal Title: Cell (In press)
  • Peer Reviewed
• [Journal Article] Biophysical characterization of O-glycosylated CD99 recognition by paired Ig-like type 2 receptors (PILR) (2008)
  • Author(s): Tabata, S., Kuroki, K., Wang, J., Kajikawa, M., Shiratori, I., Kohda, D., Arase, H. and Maenaka, K.
  • Journal Title: J. Biol. Chem. (In press)
  • Peer Reviewed
• [Journal Article] An essential role of sialylated O-linked sugar chains in the recognition of mouse CD99 by haired immunoalobulin-like type 2 receptor (PILR) (2008)
  • Author(s): Wang, J., Shiratori, I., Satoh, T., Lanier, L. L., and Arase, H.
  • Journal Title: J. Immunol. 180 Pages: 1686-1693
  • Peer Reviewed
• [Journal Article] Expression, crystallization and preliminary x-ray diffraction analysis of human paired Ig-like type 2 receptor α(PILRα) (2008)
  • Author(s): Tabata, S., Kuroki, K., Maita, N., Wang, J., Shiratori, I., Arase, H., Kohda, D., and Maenaka, K
  • Journal Title: J. Immunol. 64 Pages: 44-46
  • Peer Reviewed
• [Journal Article] Cloning of B-cell-specific tetramembrane spanning molecule BTS possessing B cell proliferation inhibitory function (2007)
  • Author(s): Suenaga, T., Arase, H., Yamasaki, S., Kohno, M., Yokosuka, T., Takeuchi, A., Hattori, T, and Saito, T.
  • Journal Title: Eur. J. Immunol. 37 Pages: 3197-3207
  • Peer Reviewed
• [Journal Article] Structural elucidation of the m157 mouse cytomegalovirus ligand for Ly49 natural killer cell receptors (2007)
  • Author(s): Adams, E. J., Juo, Z. S., Venook, R. T., Boulanger, M. J., Arase, H., Lanier, L. L., and Garcia, K. C.
  • Journal Title: Proc. Natl. Acad. Sci. USA. 104 Pages: 10128-10133
  • Peer Reviewed
• [Presentation] ペア型レセプタ-PILRを介した単純ヘルペスウィルス感染機構 (2008)
  • Author(s): 荒瀬尚
  • Organizer: 日本分子生物学会シンポジウム
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-12
• [Presentation] 単純ヘルペスウィルス感染たおけるエンベロープのO型糖鎖修飾の機能 (2008)
  • Author(s): 荒瀬尚
  • Organizer: 日本糖鎖科学コンソーシアムシンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2008-12-04
• [Presentation] 抑制化レセプターPILRを介した単純ヘルペスウィルス感染機構 (2008)
  • Author(s): 荒瀬尚
  • Organizer: 日本生体防御学会学術総会シンポジウム
  • Place of Presentation: 札幌
  • Year and Date: 2008-07-10
• [Presentation] Self and non-self recognition by inhibitory PILR (2007)
  • Author(s): Hisashi Arase
  • Organizer: 日本免疫学会総会シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2007-11-22
• [Remarks]
  • URL: http://immchem.biken.osaka-u.ac.jp
• [Remarks]
  • URL: http://immchem.biken.osaka-u.ac.jp/