新規ウイルスレセプター:抑制化PILRを介する新たなウイルス感染機構の解明

• Project Area: Matrix of Infection Phenomena
• Project/Area Number: 21022025
• 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 大阪大学, 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) ; 上堀 淳二 大阪大学, 微生物病研究所, 助教 (20432429)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥12,000,000 (Direct Cost: ¥12,000,000); Fiscal Year 2010: ¥6,000,000 (Direct Cost: ¥6,000,000); Fiscal Year 2009: ¥6,000,000 (Direct Cost: ¥6,000,000)
• Keywords: 膜融合 / 抑制化レセプター / 免疫逃避機構 / ウイルスエントリー / PILR / ヘルペスウィルス / ペア型レセプター / 免疫逃避

Research Abstract

我々は、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、HSV1のGlycoprotein B(gB)と会合し、単純ペルペスウィルスI型(HSV1)の感染の際の膜融合に重要な機能を担っていることを発見した。PILRを介した感染は、免疫応答を抑制しながら宿主細胞に侵入するという今までに知られていない全く新たなウイルス感染機構と考えられる。また、HSV-1の感染の際の膜融合にはgBとgDのレセプター双方が必要であることも初めて明らかにした。本研究では、PILRを介したHSV1の感染機構の解明や抗HSV1免疫応答におけるPILRの機能解明、PILRと同様にウイルス感染に関与する抑制化レセプターの検索を行った。その結果、PILRとgBとの相互作用にはgB上の特定の糖鎖構造が重要であることが判明した。さらに、糖ペプチドによって単純ヘルペスウイルス感染を阻害できることが明らかになった。また、単純ヘルペスのgBと結合する分子として新たにNMHC-IIAの同定に成功した。

Research Products

• [Journal Article] PANP is a novel O-glycosylated PILRα ligand expressed in neural tissues (2011)
  • Author(s): Kogure, A., Shiratori, I., Wang, J., L.Lanier, L., Arase, H.
  • Journal Title: Biochem Biophys Res Commun Volume: 405 Pages: 428-433
  • Peer Reviewed
• [Journal Article] Non-muscle myosin IIA is a functional entry receptor for herpes simplex virus-1 (2010)
  • Author(s): Arii, J., Goto, H., Suenaga, T., Oyama, M., Kozika-Hata, H., Imai, T., Minowa, A., Akashi, H., Arase, H., Kawaoka, Y., Kawaguchi, Y.
  • Journal Title: Nature Volume: 467 Pages: 859-862
  • Peer Reviewed
• [Journal Article] A Single Amino Acid Substitution in Herpes simplex virus 1 Envelope Glycoprotein B at a Site Required for Binding to the Paired Immunoglobulin-like Type 2 Receptor α (PILRα) Abrogates PILRα-dependent Viral Entry and Reduces Pathogenesis (2010)
  • Author(s): Arii, J., Wang, J., Morimoto, T., Suenaga, T., Akashi, H., Arase, H., Kawaguchi, Y.
  • Journal Title: J.Virol. Volume: 84 Pages: 10773-10783
  • Peer Reviewed
• [Journal Article] Myelin-associated glycoprotein mediates membrane fusion and entry of neurotropic herpesviruses. (2010)
  • Author(s): Suenaga, T., Satoh, T., Somboonthum, P., Kawaguchi, Y., Mori, Y., Arase, H.
  • Journal Title: Proc.Natl.Acad.Sci.USA Volume: 107 Pages: 866-871
  • Peer Reviewed
• [Journal Article] Binding and uptake of H-ferritin are mediated by human transferrin receptor-1. (2010)
  • Author(s): Li, L., Fang, C.J., Ryan, J.C., Niemi, E.C., Lebron, J.A., Bjorkman, P.J., Arase, H., Torti, F.M., Torti, S.V., Nakamura, M.C., Seaman, W.E.
  • Journal Title: Proc.Natl.Acad.Sci.USA Volume: 107 Pages: 3505-3510
  • Peer Reviewed
• [Journal Article] Binding of herpes simplex virus glycoprotein B (gB) to PILRα depends on specific sialylated O-linked glycans on gB (2009)
  • Author(s): Wang, J., Fan, F., Satoh, T., Arii, J., Lanier, L.L., Spear, P.G., Kawaguchi, Y., Arase, H.
  • Journal Title: J.Virol. Volume: 83 Pages: 13042-13045
  • Peer Reviewed
• [Journal Article] The study of regulatory T cells and NKT cells in Japan : a historical perspective. (2009)
  • Author(s): Arase, H., Seino, K.I.
  • Journal Title: Int.Immunol Volume: 21 Pages: 1101-1103
  • NAID: 10027389540
  • Peer Reviewed
• [Journal Article] Entry of herpes simplex virus 1 and other alphaherpesviruses via the paired immunoglobulin-like type 2 receptor α. (2009)
  • Author(s): Arii, J., Uema, M., Morimoto, T., Sagara, H., Akashi, H., Ono, E., Arase, H., Kawaguchi, Y
  • Journal Title: J.Virol. Volume: 83 Pages: 4520-4527
  • Peer Reviewed
• [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: J.Virol. Volume: 83 Pages: 7384-7390
  • Peer Reviewed
• [Presentation] 神経組織指向性αヘルペスウイルスのエントリーレセプター (2010)
  • Author(s): 末永忠広, 荒瀬尚
  • Organizer: 第58回日本ウイルス学会学術集会
  • Place of Presentation: 徳島県郷土文化会館(徳島市)
  • Year and Date: 2010-11-09
• [Presentation] Crucial Role of Sialic Acid Binding Receptors in Herpes Virus Infection (2010)
  • Author(s): Hisashi Arase
  • Organizer: Annual Conference of the Society for Glycobiology
  • Place of Presentation: St.Pete Beach, FL (U.S.A)(招待講演)
  • Year and Date: 2010-11-08
• [Presentation] Regulation of herpesvirus infection by paired receptors (2010)
  • Author(s): Hisashi Arase
  • Organizer: The CSI-IFReC Joint Symposium on Immunology
  • Place of Presentation: Hangzhou (China)(招待講演)
  • Year and Date: 2010-11-03
• [Presentation] Interaction between Siglec and Varicella-Zoster Virus (VZV) (2010)
  • Author(s): Tadahiro Suenaga
  • Organizer: 14th International Congress of Immunology
  • Place of Presentation: 神戸国際展示場(神戸市)
  • Year and Date: 2010-08-24
• [Presentation] Myelin-Associated Glycoprotein Associates with gB and is Involved in Membrane Fusion during Neurotropic Herpesvirus Infection (2010)
  • Author(s): Tadahiro Suenaga
  • Organizer: 35th International Herpesvirus Workshop
  • Place of Presentation: Salt Lake City, Utah (U.S.A)
  • Year and Date: 2010-07-25
• [Presentation] Crucial role of glycan binding receptors in herpesvirus infection (2010)
  • Author(s): Hisashi Arase
  • Organizer: 1st Asia Pacific Workshop
  • Place of Presentation: Seoul, (Korea)(招待講演)
  • Year and Date: 2010-07-16
• [Presentation] 新規神経指向性ヘルペスウイルスレセプタ-の同定と解析 (2010)
  • Author(s): 末永忠広、荒瀬尚
  • Organizer: 第51回日本神経学会総会
  • Place of Presentation: 東京国際フォーラム(東京)
  • Year and Date: 2010-05-21
• [Presentation] ペア型レセプターを介したヘルペスウィルス感染制御機構 (2010)
  • Author(s): 荒瀬尚
  • Organizer: 日本食品免疫学会次世代シンポジウム
  • Place of Presentation: 東京(招待講演)
  • Year and Date: 2010-01-18
• [Presentation] Regulation of herpesvirus infection by paired receptors (2009)
  • Author(s): Hisashi Arase
  • Organizer: 第39回日本免疫学会総会・学術集会
  • Place of Presentation: 大阪市(招待講演)
  • Year and Date: 2009-12-02
• [Presentation] Immune Evasion of Varicella-Zoster Virus (VZV) via Siglec-7 (2009)
  • Author(s): Tadahiro Suenaga, Fuminori Arisawa, Hisashi Arase
  • Organizer: 第39回日本免疫学会総会・学術集会
  • Place of Presentation: 大阪市
  • Year and Date: 2009-12-02
• [Presentation] PILR-L2 is a novel PILRα ligand expressed in the brain (2009)
  • Author(s): 木檜周、白鳥行大、王静、荒瀬尚
  • Organizer: 第39回日本免疫学会総会・学術集会
  • Place of Presentation: 大阪市
  • Year and Date: 2009-12-02
• [Presentation] 水痘帯状庖疹ウィルス(VZV)の新規エントリーレセプター (2009)
  • Author(s): 末永忠広、有澤史倫、佐藤毅史、Pranee Somboonthum、森康子、荒瀬尚
  • Organizer: 第57回日本ウイルス学会
  • Place of Presentation: 東京
  • Year and Date: 2009-10-26
• [Presentation] Hemopexinによる新たなインフルエンザ感染防御機構 (2009)
  • Author(s): 木檜周、大道寺智、上田真世、中屋隆明、荒瀬尚
  • Organizer: 第57回日本ウィルス学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2009-10-26
• [Presentation] Paired Immunoglobulin (Ig) Like type 2 Receptor(PILR)αによるGlycoprotein B(gB)認識機構の解明 (2009)
  • Author(s): 山口宗親、黒木喜美子、田畑栄一、真板宣夫、梶川瑞穂、尾瀬農之、中村聖子、王静、佐藤毅、荒瀬尚、前仲勝実
  • Organizer: 第57回日本ウィルス学会・学術集会
  • Place of Presentation: 東京
  • Year and Date: 2009-10-26
• [Presentation] A Varicells-Zoster Virus entry receptor that mediates membrane fusion and infection. (2009)
  • Author(s): Tadahiro Suenaga, Takeshi Satoh, Pranee Somboonthum, Yasuko Mori, Hisashi Arase.
  • Organizer: 14th International Conference on Immunobiology and Prophylaxis of Human Herpesvirus.
  • Place of Presentation: Kobe
  • Year and Date: 2009-10-06
• [Presentation] Regulation of herpesvirus infection by paired receptors (2009)
  • Author(s): Hisashi Arase
  • Organizer: The Viruses and Cells Gordon Conference
  • Place of Presentation: Lucca (Barga), Italy(招待講演)
  • Year and Date: 2009-06-09
• [Presentation] Molecular basis for recognition of Paired Immunoglobulin Like type2 Receptor (PILR) α to glycoprotein B(gB) of herpes simplex virus-1 (HSV-1) (2009)
  • Author(s): YAMAGUCHI Munechika, KUROKI Kimiko, TABATA Shigekazu, MAITA Nobuo, OSE Toyoyuki, KAJIKAWA Mizuho, NAKAMURA Seiko, WANG Jing, SATOH Takeshi, ARASE Hisashi, MAENAKA Katsumi
  • Organizer: 第39回日本免疫学会総会・学術集会
  • Place of Presentation: 大阪市
• [Remarks]
  • URL: http://immchem.biken.osaka-u.ac.jp/
• [Remarks]
  • URL: http://immchem.biken.osaka-u.ac.jp/