新興ウイルスの誕生原理と、コウモリがその自然宿主たり得る原理の解明

• Project/Area Number: 22KJ0809
• Project/Area Number (Other): 22J11578 (2022)
• Research Category: Grant-in-Aid for JSPS Fellows
• Allocation Type: Multi-year Fund (2023); Single-year Grants (2022)
• Section: 国内
• Review Section: Basic Section 49060:Virology-related
• Research Institution: The University of Tokyo
• Principal Investigator: 瓜生 慧也 東京大学, 大学院医学系研究科, 特別研究員(DC2)
• Project Period (FY): 2023-03-08 – 2024-03-31
• Project Status: Completed (Fiscal Year 2023)
• Budget Amount: ¥1,700,000 (Direct Cost: ¥1,700,000); Fiscal Year 2023: ¥800,000 (Direct Cost: ¥800,000); Fiscal Year 2022: ¥900,000 (Direct Cost: ¥900,000)
• Keywords: 新型コロナウイルス / パンデミック / 変異株 / 変異株解析

Outline of Research at the Start

本研究では、新型コロナウイルスSARS-CoV-2の異種間伝播の原理、および、コウモリがヒト病原性ウイルスの自然宿主たり得る原理を明らかにすることを目的とする。現在世界中で、SARS-CoV-2に関する研究が展開されているが、SARS-CoV-2がどのようにして誕生し、ヒトに適応進化したのかは不明である。本研究の完成時には、将来起こり得る新興・再興ウイルス感染症に人類が打ち勝つための知見の一端を得ることができる。

Outline of Annual Research Achievements

新型コロナウイルスの流行は未だ収束せず、本年度も複数の変異株が世界中で流行した。特に、2022年後半から世界的に拡がったオミクロンXBB系統（Tamura et al., Nat. Commun., 2023）がさらに多様化しており、複数のXBB系統株が各国で流行している。このような背景を踏まえ、我々は引き続き新たに出現した変異株の性状を迅速に解析することに取り組んだ。具体的にはまず、2023年初頭にアメリカを中心に流行爆発したXBB.1.5株に加え、XBB.1.16株（Yamasoba et al., Lancet Infect. Dis., 2023）、EG.5.1株（Kaku et al., Lancet Infect. Dis., 2023）、HK.3株（Kosugi et al., Lancet Microbe, 2023）など、世界各地で勢力を拡大していたいくつかのXBB系統株に着目して、その流行動態や中和抗体の効果などに関する実験結果を学術誌に報告した。さらに、夏頃に出現したXBB系統と系統的に大きく異なるBA.2.86株やその派生株の一つであるJN.1株などについてもそのウイルス学的性状を明らかにした（Uriu et al., Lancet Infect. Dis., 2023; Kaku et al., Lancet Infect. Dis., 2024）。また現在、変異株に対応したワクチンとして最も新しいXBB.1.5株対応の1価ワクチンについて、変異株に対する効果を検証した。その結果XBB.1.5株対応の1価ワクチン接種後では接種前に比べ、XBB系統株などさまざまな変異株に対しても、感染中和効果が上昇することを示した（Kosugi et al., Lancet Infect. Dis., 2024.）。

Research Products

• [Journal Article] Characteristics of the SARS-CoV-2 omicron HK.3 variant harbouring the FLip substitution (2024)
  • Author(s): Kosugi Yusuke、Plianchaisuk Arnon、Putri Olivia、Uriu Keiya、Kaku Yu、Hinay Alfredo A、Chen Luo、Kuramochi Jin、Sadamasu Kenji、Yoshimura Kazuhisa、Asakura Hiroyuki、Nagashima Mami、Ito Jumpei、Sato Kei、et al.
  • Journal Title: The Lancet Microbe Volume: 5 Issue: 4 Pages: e313-e313
  • DOI: 10.1016/s2666-5247(23)00373-7
  • Peer Reviewed / Open Access
• [Journal Article] Antiviral humoral immunity against SARS-CoV-2 omicron subvariants induced by XBB.1.5 monovalent vaccine in infection-naive and XBB-infected individuals (2024)
  • Author(s): Kosugi Yusuke、Kaku Yu、Hinay Alfredo A、Guo Ziyi、Uriu Keiya、Kihara Minoru、Saito Fumitake、Uwamino Yoshifumi、Kuramochi Jin、Shirakawa Kotaro、Takaori-Kondo Akifumi、Sato Kei
  • Journal Title: The Lancet Infectious Diseases Volume: 24 Issue: 3 Pages: e147-e148
  • DOI: 10.1016/s1473-3099(23)00784-3
  • Peer Reviewed / Open Access
• [Journal Article] Two-step evolution of HIV-1 budding system leading to pandemic in the human population (2024)
  • Author(s): Konno Yoriyuki、Uriu Keiya、Chikata Takayuki、Takada Toru、Kurita Jun-ichi、Ueda Mahoko Takahashi、Islam Saiful、Yang Tan Benjy Jek、Ito Jumpei、Aso Hirofumi、Kumata Ryuichi、Williamson Carolyn、Iwami Shingo、Takiguchi Masafumi、Nishimura Yoshifumi、Morita Eiji、Satou Yorifumi、Nakagawa So、Koyanagi Yoshio、Sato Kei
  • Journal Title: Cell Reports Volume: 43 Issue: 2 Pages: 113697-113697
  • DOI: 10.1016/j.celrep.2024.113697
  • Peer Reviewed / Open Access
• [Journal Article] Virological characteristics of the SARS-CoV-2 BA.2.86 variant (2024)
  • Author(s): Tamura Tomokazu、Mizuma Keita、Nasser Hesham、Deguchi Sayaka、Padilla-Blanco Miguel、Oda Yoshitaka、Uriu Keiya、Tolentino Jarel E.M.、Tsujino Shuhei、Suzuki Rigel、Kojima Isshu、Nao Naganori、Shimizu Ryo、Wang Lei、Tsuda Masumi、Jonathan Michael、Kosugi Yusuke、et al.
  • Journal Title: Cell Host &Microbe Volume: 32 Issue: 2 Pages: 170-180.e12
  • DOI: 10.1016/j.chom.2024.01.001
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Virological characteristics of the SARS-CoV-2 Omicron XBB.1.5 variant (2024)
  • Author(s): Tamura Tomokazu、Irie Takashi、Deguchi Sayaka、Yajima Hisano、Tsuda Masumi、Nasser Hesham、Mizuma Keita、Plianchaisuk Arnon、Suzuki Saori et al.
  • Journal Title: Nature Communications Volume: 15 Issue: 1 Pages: 1176-1176
  • DOI: 10.1038/s41467-024-45274-3
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Virological characteristics of the SARS-CoV-2 omicron XBB.1.16 variant (2023)
  • Author(s): Yamasoba Daichi、Uriu Keiya、Plianchaisuk Arnon、Kosugi Yusuke、Pan Lin、Zahradnik Jiri、Ito Jumpei、Sato Kei
  • Journal Title: The Lancet Infectious Diseases Volume: 23 Issue: 6 Pages: 655-656
  • DOI: 10.1016/s1473-3099(23)00278-5
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Convergent evolution of SARS-CoV-2 Omicron subvariants leading to the emergence of BQ.1.1 variant (2023)
  • Author(s): Ito Jumpei、Suzuki Rigel、Uriu Keiya et al.
  • Journal Title: Nature Communications Volume: 14 Issue: 1 Pages: 2671-2671
  • DOI: 10.1038/s41467-023-38188-z
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Virological characteristics of the SARS-CoV-2 XBB variant derived from recombination of two Omicron subvariants (2023)
  • Author(s): Tamura Tomokazu、Ito Jumpei、Uriu Keiya、Zahradnik Jiri、Kida Izumi、Anraku Yuki、Nasser Hesham、Shofa Maya、Oda Yoshitaka、Lytras Spyros、Nao Naganori、Itakura Yukari、Deguchi Sayaka、Suzuki Rigel...Suzuki Saori et al.
  • Journal Title: Nature Communications Volume: 14 Issue: 1 Pages: 2800-2800
  • DOI: 10.1038/s41467-023-38435-3
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Impact of Imprinted Immunity Induced by mRNA Vaccination in an Experimental Animal Model (2023)
  • Author(s): Fujita S, Uriu K, Pan L, Nao N, Tabata K, Kishimoto M, Itakura Y, Sawa H, Kida I, Tamura T; Genotype to Phenotype Japan (G2P-Japan) Consortium; Fukuhara T, Ito J, Matsuno K, Sato K.
  • Journal Title: The Journal of Infectious Diseases Volume: 228 Issue: 8 Pages: 1060-1065
  • DOI: 10.1093/infdis/jiad230
  • Peer Reviewed / Open Access
• [Journal Article] Multiple mutations of SARS-CoV-2 Omicron BA.2 variant orchestrate its virological characteristics (2023)
  • Author(s): Kimura Izumi、Yamasoba Daichi、Nasser Hesham et al.
  • Journal Title: Journal of Virology Volume: 97 Issue: 10
  • DOI: 10.1128/jvi.01011-23
  • Peer Reviewed / Open Access
• [Journal Article] Antiviral efficacy of the SARS-CoV-2 XBB breakthrough infection sera against omicron subvariants including EG.5 (2023)
  • Author(s): Kaku Yu、Kosugi Yusuke、Uriu Keiya、Ito Jumpei、Hinay Alfredo A、Kuramochi Jin、Sadamasu Kenji、Yoshimura Kazuhisa、Asakura Hiroyuki、Nagashima Mami、Sato Kei
  • Journal Title: The Lancet Infectious Diseases Volume: 23 Issue: 10 Pages: e395-e396
  • DOI: 10.1016/s1473-3099(23)00553-4
  • Peer Reviewed / Open Access
• [Journal Article] Transmissibility, infectivity, and immune evasion of the SARS-CoV-2 BA.2.86 variant (2023)
  • Author(s): Uriu Keiya、Ito Jumpei、Kosugi Yusuke、Tanaka Yuri L、Mugita Yuka、Guo Ziyi、Hinay Alfredo A、Putri Olivia、Kim Yoonjin、Shimizu Ryo、Begum MST Monira、Jonathan Michael、Saito Akatsuki、Ikeda Terumasa、Sato Kei
  • Journal Title: The Lancet Infectious Diseases Volume: 23 Issue: 11 Pages: e460-e461
  • DOI: 10.1016/s1473-3099(23)00575-3
  • Peer Reviewed / Open Access
• [Journal Article] ORF3c is expressed in SARS‐CoV‐2‐infected cells and inhibits innate sensing by targeting MAVS (2023)
  • Author(s): M?ller Martin、Herrmann Alexandra、Fujita Shigeru、Uriu Keiya、Kruth Carolin、Strange Adam、Kolberg Jan E、Schneider Markus、Ito Jumpei、M?ller Marcel A、Drosten Christian、Ensser Armin、Sato Kei、Sauter Daniel、The Genotype to Phenotype Japan (G2P‐Japan) Consortium
  • Journal Title: EMBO reports Volume: 24 Issue: 12 Pages: 57137-57137
  • DOI: 10.15252/embr.202357137
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Enhanced transmissibility, infectivity, and immune resistance of the SARS-CoV-2 omicron XBB.1.5 variant (2023)
  • Author(s): Uriu et al.
  • Journal Title: Lancet Infectious Diseases Volume: 23 Issue: 3 Pages: 280-281
  • DOI: 10.1016/s1473-3099(23)00051-8
  • Peer Reviewed / Open Access
• [Journal Article] The SARS-CoV-2 Lambda variant exhibits enhanced infectivity and immune resistance (2022)
  • Author(s): Kimura Izumi、Kosugi Yusuke、Wu Jiaqi、other 17 authors、Saito Akatsuki、Nakagawa So、Sato Kei
  • Journal Title: Cell Reports Volume: 38 Issue: 2 Pages: 110218-110218
  • DOI: 10.1016/j.celrep.2021.110218
  • NAID: 120007183813
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Attenuated fusogenicity and pathogenicity of SARS-CoV-2 Omicron variant (2022)
  • Author(s): Suzuki Rigel、Yamasoba Daichi、Kimura Izumi、Wang Lei他
  • Journal Title: Nature Volume: 603 Issue: 7902 Pages: 700-705
  • DOI: 10.1038/s41586-022-04462-1
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Characterization of the Immune Resistance of Severe Acute Respiratory Syndrome Coronavirus 2 Mu Variant and the Robust Immunity Induced by Mu Infection (2022)
  • Author(s): Uriu Keiya et al.
  • Journal Title: The Journal of Infectious Diseases Volume: 00 Issue: 7 Pages: 00-00
  • DOI: 10.1093/infdis/jiac053
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Virological characteristics of the SARS-CoV-2 Omicron BA.2 spike (2022)
  • Author(s): Yamasoba Daichi、Kimura Izumi、Nasser Hesham他
  • Journal Title: Cell Volume: 未定 Issue: 12 Pages: 2103-2115
  • DOI: 10.1016/j.cell.2022.04.035
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Neutralisation sensitivity of SARS-CoV-2 omicron subvariants to therapeutic monoclonal antibodies (2022)
  • Author(s): Yamasoba Daichi、Kosugi Yusuke、Kimura Izumi、Fujita Shigeru、Uriu Keiya、Ito Jumpei、Sato Kei
  • Journal Title: The Lancet Infectious Diseases Volume: 22 Issue: 7 Pages: 942-943
  • DOI: 10.1016/s1473-3099(22)00365-6
  • Peer Reviewed / Open Access
• [Journal Article] Virological characteristics of the SARS-CoV-2 Omicron BA.2 subvariants, including BA.4 and BA.5 (2022)
  • Author(s): Kimura et al.
  • Journal Title: Cell Volume: 185 Issue: 21 Pages: 3992-4007
  • DOI: 10.1016/j.cell.2022.09.018
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Virological characteristics of the SARS-CoV-2 Omicron BA.2.75 variant (2022)
  • Author(s): Saito et al.
  • Journal Title: Cell Host & Microbe Volume: 30 Issue: 11 Pages: 1540-1540
  • DOI: 10.1016/j.chom.2022.10.003
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The SARS-CoV-2 spike S375F mutation characterizes the Omicron BA.1 variant (2022)
  • Author(s): Kimura Izumi, et al
  • Journal Title: iScience Volume: 25 Issue: 12 Pages: 105720-105720
  • DOI: 10.1016/j.isci.2022.105720
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Enhanced fusogenicity and pathogenicity of SARS-CoV-2 Delta P681R mutation (2021)
  • Author(s): Saito Akatsuki、Irie Takashi、Suzuki Rigel、Maemura Tadashi、Nasser Hesham、Uriu Keiya、Kosugi Yusuke、Other 43 authors、Tanaka Shinya、Nakagawa So、Ikeda Terumasa、Fukuhara Takasuke、Kawaoka Yoshihiro、Sato Kei、The Genotype to Phenotype Japan (G2P-Japan) Consortium
  • Journal Title: Nature Volume: 602 Issue: 7896 Pages: 300-306
  • DOI: 10.1038/s41586-021-04266-9
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Immune resistance of newly emerging SARS-CoV-2 Omicron variants. (2023)
  • Author(s): ○Keiya Uriu, Jumpei Ito, Maya Shofa, Ryo Shimizu, MST Monira Begum, Shigeru Fujita, Yusuke Kosugi, The Genotype to Phenotype Japan (G2P-Japan) Consortium, Akatsuki Saito, Terumasa Ikeda, Kei Sato.
  • Organizer: U.S.-Japan Cooperative Medical Science Program (USJCMSP) International Conference on Emerging Infectious Diseases in the Pacific Rim
  • Int'l Joint Research
• [Presentation] Immune resistance of newly emerging SARS-CoV-2 Omicron variants. (2023)
  • Author(s): ○Keiya Uriu, Jumpei Ito, Maya Shofa, Ryo Shimizu, MST Monira Begum, Shigeru Fujita, Yusuke Kosugi, The Genotype to Phenotype Japan (G2P-Japan) Consortium, Akatsuki Saito, Terumasa Ikeda, Kei Sato.
  • Organizer: XVIth International Nidovirus Symposium
  • Int'l Joint Research
• [Presentation] オミクロンBA.2のウイルス学的特徴を規定する変異の探索 (2023)
  • Author(s): ○瓜生慧也, 木村出海, 山岨大智, Hesham Nasser, 伊藤駿, Wu Jiaqi, 藤田滋, 佐々木慈英, 田村友和, 鈴木理滋, 出口清香, The Genotype to Phenotype Japan (G2P-Japan) Consortium, 白川康太郎, 高山和雄, 入江崇, 橋口隆生, 中川草, 福原崇介, 齊藤暁, 池田輝政, 佐藤佳.
  • Organizer: 第1回新型コロナウイルス研究集会
• [Presentation] オミクロンBA.2のウイルス学的特徴を規定する変異の探索 (2023)
  • Author(s): ○瓜生慧也, 木村出海, 山岨大智, Hesham Nasser, 伊藤駿, Wu Jiaqi, 藤田滋, 佐々木慈英, 田村友和, 鈴木理滋, 出口清香, The Genotype to Phenotype Japan (G2P-Japan) Consortium, 白川康太郎, 高山和雄, 入江崇, 橋口隆生, 中川草, 福原崇介, 齊藤暁, 池田輝政, 佐藤佳.
  • Organizer: 第17回ウイルス学キャンプ
• [Presentation] SARS-CoV-2オミクロン関連変異株の進化と免疫逃避 (2023)
  • Author(s): ○瓜生慧也, 伊東潤平, マヤショーファ, 清水凌, MST Monira Begum, 山岨大智, Arnon Plianchaisuk, 藤田滋, 小杉優介, The Genotype to Phenotype Japan (G2P-Japan) Consortium, 齊藤暁, 池田輝政, 佐藤佳.
  • Organizer: 第70回日本ウイルス学会学術集会
• [Presentation] Immune resistance of newly emerging SARS-CoV-2 Omicron variants. (2023)
  • Author(s): ○Keiya Uriu, Jumpei Ito, Maya shofa, Ryo Shimizu, MST Monira Begum, Shigeru Fujita, Yusuke Kosugi, Yu Kaku, Alfredo A. Hinay Jr., The Genotype to Phenotype Japan (G2P-Japan) Consortium, Akatsuki Saito, Terumasa Ikeda, Kei Sato.
  • Organizer: The 29th East Asia Joint Symposium
  • Int'l Joint Research
• [Presentation] Insights into the cleavage of SARS-CoV-2 Spike protein, fusogenicity and pathogenicity. (2022)
  • Author(s): Keiya Uriu1, Hesham Nasser2, Rigel Suzuki3, Mai Kishimoto4, G2P-Japan Consortium, Hirofumi Sawa4, Takasuke Fukuhara3, Terumasa Ikeda2, Kei Sato1.
  • Organizer: 第69回ウイルス学会
• [Presentation] Immune resistance of newly emerging SARS-CoV-2 variants (2022)
  • Author(s): ○Keiya Uriu1, Jumpei Ito1, Shigeru Fujita1, Yusuke Kosugi1, The Genotype to Phenotype Japan (G2P-Japan) Consortium, Kei Sato1.
  • Organizer: International Conference of the Emerging Iinfectiou Diseases
  • Int'l Joint Research