Mechanisms of viral entry and membrane fusion of herpesvirus

• Project/Area Number: 25460565
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Virology
• Research Institution: Osaka University
• Principal Investigator: Suenaga Tadahiro 大阪大学, 微生物病研究所, 准教授 (20396675)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: ヘルペスウイルス / 水痘帯状疱疹ウイルス / ヒトヘルペスウイルス６型 / 膜融合 / エントリー / CRISPR/Cas9 / 糖鎖 / シアル酸 / グリコプロテイン / 糖鎖修飾 / CRISPR-Cas9 / ゲノム編集

Outline of Final Research Achievements

We identified and analyzed host receptors for varicella-zoster virus (VZV) entry such as MAG. We reported that sugar chain of VZV gB is essential for entry and identified the glycosylation sites on gB.
The complex of gH, gL, gQ1 and gQ2 of human herpesvirus-6 (HHV-6) is indispensable for HHV-6 entry and binds to a host receptor CD46. We also identified a host factor H6IR that inhibits the binding of the complex to CD46 and that blocks HHV-6 entry.
We developed a simple method based on CRISPR/Cas9 system for genome-editing of large DNA virus such as herpes simplex virus.

Research Products

• [Journal Article] The effect of rhododendrol inhibition of NF-κB on melanocytes in the presence of tyrosinase. (2016)
  • Author(s): Arase N, Yang L, Tanemura A, Yang F, Suenaga T, Arase H, Katayama I.
  • Journal Title: J Dermatol Sci. Volume: 83 Issue: 2 Pages: 157-159
  • DOI: 10.1016/j.jdermsci.2016.05.002
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] LILRA2 is an innate immune sensor for microbially cleaved immunoglobulins. (2016)
  • Author(s): Hirayasu K, Saito F, Suenaga T, Shida K, Arase N, Oikawa K, Yamaoka T, Murota H, Chibana H, Nagai H, Nakamura Y, Katayama I, Colonna M, Arase H.
  • Journal Title: Nature Microbiol. Volume: 未定
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Sialic Acids on Varicella-Zoster Virus Glycoprotein B Are Required for Cell-Cell Fusion. (2015)
  • Author(s): Suenaga T, Matsumoto M, Arisawa F, Kohyama M, Hirayasu K, Mori Y, Arase H.
  • Journal Title: J Biol Chem. Volume: 290 Issue: 32 Pages: 19833-19843
  • DOI: 10.1074/jbc.m114.635508
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] β2-glycoprotein I/ HLA class II complexes are novel autoantigens in antiphospholipid syndrome. (2015)
  • Author(s): Tanimura K, Jin H, Suenaga T, Morikami S, Arase N, Kishida K, Hirayasu K, Kohyama M, Ebina Y, Yasuda S, Horita T, Takasugi K, Ohmura K, Yamamoto K, Katayama I, Sasazuki T, Lanier LL, Atsumi T, Yamada H, Arase H.
  • Journal Title: Blood Volume: 125 Issue: 18 Pages: 2835-2844
  • DOI: 10.1182/blood-2014-08-593624
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Negative regulation of DSS-induced experimental colitis by PILRα. (2015)
  • Author(s): Kishida, K., Kohyama, M., Kurashima, Y., Kogure, Y., Wang, J., Hirayasu, K., Suenaga, T., Kiyono, H., Kunisawa, J. and Arase, H.
  • Journal Title: Int. Immunol. Volume: - Issue: 6 Pages: 307-314
  • DOI: 10.1093/intimm/dxv004
  • Peer Reviewed / Open Access
• [Journal Article] Engineering large viral DNA genomes using the CRISPR-Cas9 system. (2014)
  • Author(s): Suenaga T, Kohyama M, Hirayasu K, Arase H.
  • Journal Title: Microbiol Immunol. Volume: 58（9） Issue: 9 Pages: 513-522
  • DOI: 10.1111/1348-0421.12180
  • NAID: 40020207309
  • Peer Reviewed
• [Journal Article] Autoantibodies to IgG/HLA class II complexes are associated with rheumatoid arthritis susceptibility (2014)
  • Author(s): Jin H, Arase N, Hirayasu K, Kohyama M, Suenaga T, Saito F, Tanimura K, Matsuoka S, Ebina K, Shi K, Toyama-Sorimachi N, Yasuda S, Horita T, Hiwa R, Takasugi K, Ohmura K, Yoshikawa H, Saito T, Atsumi T, Sasazuki T, Katayama I, Lanier LL, Arase H
  • Journal Title: Proceedings of National Academy of Science USA Volume: 111 Issue: 10 Pages: 3787-3792
  • DOI: 10.1073/pnas.1401105111
  • Peer Reviewed / Open Access
• [Journal Article] Herpesvirus 6 glycoproteins B (gB), gH, gL, and gQ are necessary and sufficient for cell-to-cell fusion. (2013)
  • Author(s): Tanaka Y, Suenaga T, Matsumoto M, Seya T, Arase H.
  • Journal Title: J Virol. Volume: 87(19) Issue: 19 Pages: 10900-10903
  • DOI: 10.1128/jvi.01427-13
  • Peer Reviewed
• [Presentation] ヒトヘルペスウイルス6型に結合する新規宿主分子の同定と機能解析 (2016)
  • Author(s): Tadahiro Suenaga, Yuriko Muramatsu , Yasuko Mori, Hisashi Arase
  • Organizer: 第64回日本ウイルス学会学術集会
  • Place of Presentation: 札幌コンベンションセンター（北海道）
  • Year and Date: 2016-10-23
• [Presentation] 糖鎖を利用した単純ヘルペスウイルス、水痘帯状疱疹ウイルスの神経組織感染制御法の開発 (2016)
  • Author(s): 末永忠広、荒瀬尚
  • Organizer: 第21回日本神経感染症学会総会・学術大会
  • Place of Presentation: 金沢東急ホテル（石川）
  • Year and Date: 2016-10-21
• [Presentation] Structure of Varicella-Zoster Virus and Herpes Simplex Virus Glycoproteins B (gB) and gH Required for Membrane Fusion (2016)
  • Author(s): Suenaga Tadahiro
  • Organizer: 第15回あわじしま感染症・免疫フォーラム
  • Place of Presentation: 淡路夢舞台国際会議場（兵庫）
  • Year and Date: 2016-09-06
  • Int'l Joint Research
• [Presentation] HHV-6 dH/gL/gQ1/gQ2と結合する骨髄系細胞分子H6IR1の同定 (2016)
  • Author(s): 末永 忠広、村松 佑理子、森 康子、荒瀬 尚
  • Organizer: 第30回ヘルペスウイルス研究会
  • Place of Presentation: セミナーハウス クロス・ウェーブ府中（東京）
  • Year and Date: 2016-06-16
• [Presentation] Functional analysis of sialic acids on varicella-zoster virus glycoprotein B (2015)
  • Author(s): Tadahiro Suenaga, Maki Katsumoto, Fuminori Arisawa, Masako Kohyama, Kouyuki, Hirayasu, Yasuko Mori, Hisashi Arase
  • Organizer: 第63回日本ウイルス学会学術集会
  • Place of Presentation: 福岡国際会議場（福岡）
  • Year and Date: 2015-11-23
• [Presentation] MHC class II molecules expose autoantibody epitopes on autoantigens (2015)
  • Author(s): Jin Hui, Arase Noriko, Matsuoka Sumiko, Hirayasu Kouyuki, Kohyama Masako, Suenaga Tadahiro, Sasazuki Takehiko, Arase Hisashi
  • Organizer: 第44日本免疫学会学術集会
  • Place of Presentation: 札幌コンベンションセンター（北海道）
  • Year and Date: 2015-11-18
• [Presentation] Myeloperoxidase/HLA class II complexes are targets for autoantibodies in ANCA-associated vasculitis (2015)
  • Author(s): Hiwa Ryosuke, Ohmura Koichiro, Arase Noriko, Jin Hui, Hirayasu Kouyuki, Kohyama Masako, Suenaga Tadahiro, Saito Fumiji, Iwatani Hirotsugu, Atsumi Tatsuya, Terao Chikashi, Mimori Tsuneyo, Arase Hisashi
  • Organizer: 第44日本免疫学会学術集会
  • Place of Presentation: 札幌コンベンションセンター（北海道）
  • Year and Date: 2015-11-18
• [Presentation] DIR is an innate immune sensor for microbially cleaved immunoglobulins (2015)
  • Author(s): Hirayasu Kouyuki, Saito Fumiji, Suenaga Tadahiro, Shida Kyoko, Arase Noriko, Oikawa Keita, Yamaoka Toshifumi, Murota Hiroyuki, Chibana Hiroji, Nagai Hiroki, Nakamaru Yuji, Katayama Ichiro, Arase Hisashi
  • Organizer: 第44日本免疫学会学術集会
  • Place of Presentation: 札幌コンベンションセンター（北海道）
  • Year and Date: 2015-11-18
• [Presentation] MPO/HLA classⅡ複合体は顕微鏡的多発血管炎における自己抗体の標的である (2015)
  • Author(s): 日和良介, 大村浩一郎, 荒瀬規子, 金暉, 平安恒幸, 香山雅子, 末永忠広, 齋藤史路, 岩谷博次, 渥美達也, 寺尾知可史, 三森経世, 荒瀬尚
  • Organizer: 第43回日本臨床免疫学会総会
  • Place of Presentation: 神戸国際会議場（兵庫）
  • Year and Date: 2015-10-22
• [Presentation] Sialic acids on varicella-zoster virus glycoprotein B required for cell–cell fusion (2015)
  • Author(s): Tadahiro Suenaga, Yasuko Mori and Hisashi Arase
  • Organizer: 第14回あわじしま感染症・免疫フォーラム
  • Place of Presentation: 淡路夢舞台国際会議場（兵庫）
  • Year and Date: 2015-09-08
• [Presentation] Sialic acids on varicella-zoster virus glycoprotein B required for cell–cell fusion (2015)
  • Author(s): Tadahiro Suenaga, Yasuko Mori and Hisashi Arase
  • Organizer: 40th Annual International Herpesvirus Workshop
  • Place of Presentation: Boise (U.S.A.)
  • Year and Date: 2015-07-25
  • Int'l Joint Research
• [Presentation] 水痘帯状疱疹ウイルス（VZV）感染における糖鎖機能の解析 (2015)
  • Author(s): 末永 忠広、森 康子、荒瀬 尚
  • Organizer: 第２９回ヘルペスウイルス研究会
  • Place of Presentation: 長崎にっしょうかん（長崎）
  • Year and Date: 2015-06-04
• [Presentation] Myeloperoxidase/HLA class II complexes are targets for autoantibodies in microscopic polyangiitis. (2014)
  • Author(s): Hiwa Ryosuke, Ohmura Koichiro, Arase Noriko, Jin Hui, Hirayasu Kouyuki, Kohayama Masako, Suenaga Tadahiro, Matsuoka Sumiko, Iwatani Hirotsugu, Atsumi Tatsuya, Terao Chikashi, Mimori Tsuneyo, Arase Hisashi
  • Organizer: 第43回日本免疫学会学術集会
  • Place of Presentation: 国立京都国際会館（京都）
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] MHC class II-restricted recognition of self-antigen/MHC class II complexes by autoantibodies (2014)
  • Author(s): Jin Hui, Arase Noriko, Matsuoka Sumiko, Hirayasu Kouyuki, Kohayama Masako, Suenaga Tadahiro, Nakamaru Yuji, Imatani Yoshinori, Katayama Ichiro, Arase Hisashi
  • Organizer: 第43回日本免疫学会学術集会
  • Place of Presentation: 国立京都国際会館（京都）
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] CRISPR/Cas9システムを用いた DNA ウイルスのゲノム改変 (2014)
  • Author(s): 末永忠広、荒瀬尚
  • Organizer: 第62回日本ウイルス学会学術集会
  • Place of Presentation: パシフィコ横浜（横浜）
  • Year and Date: 2014-11-10 – 2014-11-12
• [Presentation] Engineering of large viral DNA genomes using the CRISPR-Cas9 system (2014)
  • Author(s): Tadahiro Suenaga, Hisashi Arase
  • Organizer: 第13回あわじしま感染症・免疫フォーラム
  • Place of Presentation: 奈良県新公会堂（奈良市）
  • Year and Date: 2014-09-23 – 2014-09-26
• [Presentation] "Sialic Acids on N-glycosylated VZV gB are Required for Membrane Fusion Mediated by Myelin-associated Glycoprotein (MAG) " (2014)
  • Author(s): Tadahiro Suenaga, Fuminori Arisawa, Maki Matsumoto, Hisashi Arase
  • Organizer: The 39th Annual International Herpesvirus Workshop (IHW2014)
  • Place of Presentation: Kobe International Exhibition Hall（神戸市）
  • Year and Date: 2014-07-19 – 2014-07-23
• [Presentation] Engineering of large DNA virus genome using CRISPR-Cas9 system (2014)
  • Author(s): 末永忠広、荒瀬尚
  • Organizer: 感染研GSC×新学術領域感染コンピ 研究交流会
  • Place of Presentation: 国立感染症研究所 戸山庁舎（東京）
  • Year and Date: 2014-07-12
• [Presentation] Autoantibodies in Rheumatoid Arthritis Specifically Recognize IgG Heavy Chain Complexed with HLA-DR, Which is Strongly Associated with Rheumatoid Arthritis Susceptibility. (2014)
  • Author(s): Jin H, Arase N, Hirayasu K, Kohyama M, Suenaga T, Saito F, Tanimura K, Matsuoka S, Ebina K, Shi K, Toyama-Sorimachi N, Yasuda S, Horita T, Hiwa R, Takasugi K, Ohmura K, Yoshikawa H, Saito T, Atsumi T, Sasazuki T, Katayama I, Lanier LL, Arase H.
  • Organizer: The 15th Annual European Congress of Rheumatology EULAR 2014
  • Place of Presentation: Paris(France)
  • Year and Date: 2014-06-11 – 2014-06-14
• [Presentation] Rheumatoid factor binding to IgG heavy chain presented on HLA-DR is associated with Rheumatoid Arthritis susceptibility
  • Author(s): Jin Hui, Arase Noriko, Kohayama Masako, Saito Fumiji, Hirayasu Kouyuki, Matsumoto Maki, Shida Kyoko, Suenaga Tadahiro, Saito Takashi, Katayama Ichiro, Lanier Lewis L., Arase Hisashi
  • Organizer: 第42回日本免疫学会学術集会
  • Place of Presentation: 幕張メッセ（千葉市）
• [Presentation] β2-glycoprotein I presented on MHC class II molecules are recognized by autoantibodies in antiphospholipid syndrome
  • Author(s): Tanimura Kenji, Suenaga Tadahiro, Jin Hui, Hirayasu Kouyuki, Arase Noriko, Kohayama Masako, Ebina Yasuhiko, Yasuda Shinsuke, Horita Tetsuya, Katayama Ichiro, Atsumi Tatsuya, Yamada Hideo, Arase Hisashi
  • Organizer: 第42回日本免疫学会学術集会
  • Place of Presentation: 幕張メッセ（千葉市）
• [Presentation] PILRα negatively regulates DSS induced experimental colitis
  • Author(s): Kishida Kazuki, Kohyama Masako, Kurashima Yosuke, Wang Jing, Hirayasu Kouyuki, Suenaga Tadahiro, Kiyono Hiroshi, Kunisawa Jun, Arase Hisashi
  • Organizer: 第42回日本免疫学会学術集会
  • Place of Presentation: 幕張メッセ（千葉市）
• [Presentation] 水痘帯状疱疹ウイルス（VZV）の膜融合メカニズムの解析
  • Author(s): 末永忠広、森康子、荒瀬尚
  • Organizer: 第61回日本ウイルス学会学術集会
  • Place of Presentation: 神戸国際会議場（神戸市）
• [Presentation] Herpesvirus 6 Glycoprotein B (gB), gH, gL and gQ are Necessary and Sufficient forCell-to-Cell Fusion
  • Author(s): Tadahiro Suenaga, Yuki Tanaka, Misako Matsumoto, Tsukasa Seya, Hisashi Arase
  • Organizer: 38th International Herpesvirus Workshop
  • Place of Presentation: Grand Rapids, Michigan, USA
• [Presentation] 水痘帯状疱疹ウイルス（VZV）glycoprotein H (gH)受容体の解析
  • Author(s): 末永忠広、松本麻紀、有澤史倫、森康子、荒瀬尚
  • Organizer: 第28回ヘルペスウイルス研究会
  • Place of Presentation: 淡路夢舞台国際会議場（淡路市）
• [Remarks] 大阪大学微生物病研究所免疫化学分野ホームページ
  • URL: http://immchem.biken.osaka-u.ac.jp
• [Remarks] 免疫化学分野ホームページ
  • URL: http://immchem.biken.osaka-u.ac.jp
• [Remarks] 免疫化学分野ホームページ
  • URL: http://immchem.biken.osaka-u.ac.jp/