Identification and characterization of host cellular factors involved in rabies virus infection

• Project/Area Number: 15K07716
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Veterinary medical science
• Research Institution: Hokkaido University
• Principal Investigator: Sasaki Michihito 北海道大学, 人獣共通感染症リサーチセンター, 特任助教 (70609403)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 狂犬病ウイルス / 宿主因子 / スクリーニング / RNAi / ヘパラン硫酸 / 吸着因子 / ウイルス表面糖タンパク / 病原性解析 / 細胞吸着 / 網羅的解析

Outline of Final Research Achievements

Cellular host factors play critical roles in virus infection. To investigate the host factors involved in rabies virus infection, we have performed a large scale of RNAi screening and found 28 host genes. Next, we revealed that cellular heparan sulfate supports rabies virus attachment and subsequent entry into cells. The direct binding between rabies virus glycoprotein and heparan sulfate was demonstrated. The molecular mechanism of the interaction between rabies virus glycoprotein and heparan sulfate was analyzed in detail. Collectively, our study identified host factors potentially involved in rabies virus infection, and highlights a previously undescribed role of heparan sulfate as an attachment factor of rabies virus infection.

Research Products

• [Int'l Joint Research] University College Dublin(Ireland)
• [Journal Article] The Role of Heparan Sulfate Proteoglycans as an Attachment Factor for Rabies Virus Entry and Infection (2018)
  • Author(s): Sasaki Michihito、Anindita Paulina D、Ito Naoto、Sugiyama Makoto、Carr Michael、Fukuhara Hideo、Ose Toyoyuki、Maenaka Katsumi、Takada Ayato、Hall William W、Orba Yasuko、Sawa Hirofumi
  • Journal Title: The Journal of Infectious Diseases Volume: 印刷中 Issue: 11 Pages: 1740-1749
  • DOI: 10.1093/infdis/jiy081
  • NAID: 120006577374
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Ribavirin-related compounds exert in vitro inhibitory effects toward rabies virus (2018)
  • Author(s): Anindita Paulina D.、Sasaki Michihito、Okada Kazuma、Ito Naoto、Sugiyama Makoto、Saito-Tarashima Noriko、Minakawa Noriaki、Shuto Satoshi、Otsuguro Satoko、Ichikawa Satoshi、Matsuda Akira、Maenaka Katsumi、Orba Yasuko、Sawa Hirofumi
  • Journal Title: Antiviral Research Volume: 154 Pages: 1-9
  • DOI: 10.1016/j.antiviral.2018.03.011
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Generation of recombinant rabies viruses encoding NanoLuc luciferase for antiviral activity assays (2016)
  • Author(s): Anindita PD, Sasaki M, Nobori H, Sato A, Carr M, Ito N, Sugiyama M, Orba Y, Sawa H
  • Journal Title: Virus Research Volume: 215 Pages: 121-128
  • DOI: 10.1016/j.virusres.2016.02.002
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Distinct lineages of bufavirus in wild shrews and nonhuman primates (2015)
  • Author(s): Sasaki M, Orba Y, Anindita PD, Ishii A, Ueno K, Hang’ombe BM, Mweene AS, Ito K, Sawa H
  • Journal Title: Emerging Infectious Diseases Volume: 21 Issue: 7 Pages: 1230-1233
  • DOI: 10.3201/eid2107.141969
  • NAID: 120005649122
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Characterization of heparan sulfate as the attachment factor for rabies virus infection (2017)
  • Author(s): Michihito Sasaki, Paulina D. Anindita, Naoto Ito, Makoto Sugiyama, Hideo Fukuhara, Toyoyuki Ose, Katsumi Maenaka, Yasuko Orba, Hirofumi Sawa
  • Organizer: 第65回日本ウイルス学会学術集会
• [Presentation] Antiviral activity of ribavirin related compounds against rabies virus in vitro (2017)
  • Author(s): Paulina D. Anindita, Michihito Sasaki, Naoto Ito, Makoto Sugiyama, Noriaki inakawa Satoshi Shuto, Satoko Otsuguro, Satoshi Ichikawa, Akira Matsuda, Katsumi Maenaka, Yasuko Orba, Hirofumi Sawa
  • Organizer: 第65回日本ウイルス学会学術集会
• [Presentation] 狂犬病ウイルスの細胞吸着に関与する宿主因子の解析 (2017)
  • Author(s): 佐々木 道仁, Anindita Paulina D., 伊藤 直人, 杉山 誠, 福原 秀雄, 尾瀬 農之, 前仲 勝実, 澤 洋文
  • Organizer: 第160回日本獣医学会学術集会
• [Presentation] Examination of antiviral activity of 5-ethynyl-1-ribofuranosylimidazole-4-carboxamide (EICAR) against rabies virus in vitro (2017)
  • Author(s): Anindita Paulina D.、佐々木 道仁、伊藤 直人、杉山 誠、南川 典昭、周東 智、乙黒 聡子、市川 聡、松田 彰、前仲 勝実、大場 靖子、澤 洋文
  • Organizer: 第160回日本獣医学会学術集会
• [Presentation] ヘパラン硫酸を介した狂犬病ウイルスの細胞吸着機構の解析 (2016)
  • Author(s): 佐々木 道仁, Anindita D. Paulina, 伊藤 直人, 杉山 誠, 福原 秀雄, 尾瀬 農之, 前仲 勝実, 大場 靖子, 澤 洋文
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-11-30
• [Presentation] Establishment of a combinatory compound screening assay to identify rabies virus antivirals (2016)
  • Author(s): Paulina Duhita Anindita, Michihito Sasaki, Haruaki Nobori, Akihiko Sato, Michael Carr, Naoto Ito, Makoto Sugiyama, Yasuko Orba, Hirofumi Sawa
  • Organizer: The 4th Sapporo Summer Seminar for One Health (SaSSOH)
  • Place of Presentation: 北海道大学（北海道札幌市）
  • Year and Date: 2016-09-20
• [Presentation] Establishment of antiviral compound screening assay employing recombinant rabies viruses encoding NanoLuc luciferase. (2016)
  • Author(s): Paulina Duhita Anindita, Michihito Sasaki, Haruaki Nobori, Akihiko Sato, Michael Carr, Naoto Ito, Makoto Sugiyama, Yasuko Orba, Hirofumi Sawa
  • Organizer: 第15回狂犬病研究会
  • Place of Presentation: 水明館（岐阜県下呂市）
  • Year and Date: 2016-04-03
• [Presentation] Identification of distinct lineages of parvovirus in wildlife (2015)
  • Author(s): 佐々木道仁、大場靖子、Anindita D. Paulina、石井秋宏、伊藤公人、澤洋文
  • 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（福岡県福岡市）
  • Year and Date: 2015-11-22
• [Presentation] Recombinant Rabies Viruses Expressing NanoLuc Luciferase for Antiviral Activity Assays (2015)
  • Author(s): Paulina D. ANINDITA, Michihito SASAKI, Haruaki NOBORI, Akihiko SATO, Naoto ITO, Makoto SUGIYAMA, Yasuko ORBA, Hirofumi SAWA
  • 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（福岡県福岡市）
  • Year and Date: 2015-11-22
• [Presentation] Recombinant Rabies Viruses Expressing NanoLuc Luciferase for Identification of Novel Antiviral Compounds (2015)
  • Author(s): Paulina D. ANINDITA, Michihito SASAKI, Haruaki NOBORI, Akihiko SATO, Naoto ITO, Makoto SUGIYAMA, Yasuko ORBA, Hirofumi SAWA
  • Organizer: 3rd Sapporo Summer Seminar for One Health
  • Place of Presentation: 北海道大学（北海道札幌市）
  • Year and Date: 2015-09-16
  • Int'l Joint Research
• [Presentation] Recombinant Rabies Luciferase Viruses for Identification of Novel Antiviral Agents (2015)
  • Author(s): Paulina D. ANINDITA, Michihito SASAKI, Haruaki NOBORI, Akihiko SATO, Naoto ITO, Makoto SUGIYAMA, Yasuko ORBA, Hirofumi SAWA
  • Organizer: 14th Awaji International Forum on Infection and Immunity
  • Place of Presentation: 淡路夢舞台国際会議場（兵庫県淡路市）
  • Year and Date: 2015-09-08
  • Int'l Joint Research
• [Presentation] 野生動物が保有するウイルスの探索と性状解析 (2015)
  • Author(s): 佐々木道仁
  • Organizer: 第158回日本獣医学会学術集会
  • Place of Presentation: 北里大学（青森県十和田市）
  • Year and Date: 2015-09-07
• [Presentation] 野生動物から検出された新規パルボウイルスの系統解析 (2015)
  • Author(s): 佐々木道仁、大場靖子、Anindita D. Paulina、石井秋宏、伊藤公人、澤洋文
  • Organizer: 第158回日本獣医学会学術集会
  • Place of Presentation: 北里大学（青森県十和田市）
  • Year and Date: 2015-09-07
• [Remarks] 北海道大学人獣共通感染症リサーチセンター 分子病態・診断部門ホームページ
  • URL: http://www.czc.hokudai.ac.jp/pathobiol/
• [Remarks] 北海道大学人獣共通感染症リサーチセンター分子病態・診断部門ホームページ
  • URL: http://www.czc.hokudai.ac.jp/pathobiol/