Investigation of virus infection dynamics through comprehensive multi-omics approach

• Project/Area Number: 18H02662
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 49060:Virology-related
• Research Institution: The University of Tokyo
• Principal Investigator: 佐藤 佳 東京大学, 医科学研究所, 准教授 (10593684)
• Co-Investigator(Kenkyū-buntansha): 中岡 慎治 北海道大学, 先端生命科学研究院, 准教授 (30512040) ; 鈴木 穣 東京大学, 大学院新領域創成科学研究科, 教授 (40323646) ; 城口 克之 国立研究開発法人理化学研究所, 生命機能科学研究センター, チームリーダー (00454059)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000); Fiscal Year 2021: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2020: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2019: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2018: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
• Keywords: ウイルス学 / システムウイルス学 / マルチオミクス / ウイルス感染 / エイズウイルス / ウイルス感染症 / HIV

Outline of Annual Research Achievements

本年度では、生体内におけるHIV-1感染細胞の性状の多角的な解析に取り組んだ。HIV-1感染ヒト化マウスとマルチオミクス解析を実施し、生体内における 「真の」HIV-1感染細胞の特徴を多角的に描き出すことに成功した。本研究で用いた研究手法は、きわめて汎用的であり、さまざまなウイルス研究への応用が可能である。つまり本研究は、ウイルスと宿主の新たな関係性の一端を明らかにした研究であり、また、ウイルスと宿主の相互作用のさらなる解明や、エイズの制圧法の開発に向けた基礎学術基盤の形成に直結する研究であると言える。以上の研究成果を、学術論文にまとめ、Cell Reports誌にcorresponding authorとして発表した。さらに、本研究を通して構築した解析方法を駆使し、新型コロナウイルスに関する研究も実施し、複数の学術論文をcorresponding authorとして発表した。具体的には、出現が続く新型コロナウイルスの変異株（デルタ株、ラムダ株、ミュー株、オミクロン株）のウイルス学的性状を包括的に解析し、それらを世界に先駆けて解明した。

Research Progress Status

令和3年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

令和3年度が最終年度であるため、記入しない。

Research Products

• [Int'l Joint Research] ウルム大学/チュービンゲン大学(ドイツ)
• [Int'l Joint Research] サンフランシスコ・デ・キト大学(エクアドル)
• [Int'l Joint Research] ワイツマン研究所(イスラエル)
• [Int'l Joint Research] グラスゴー大学/ケンブリッジ大学(英国)
• [Int'l Joint Research] ウィスコンシン大学(米国)
• [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 Pages: 110218-110218
  • DOI: 10.1016/j.celrep.2021.110218
  • NAID: 120007183813
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Altered TMPRSS2 usage by SARS-CoV-2 Omicron impacts infectivity and fusogenicity (2022)
  • Author(s): Meng Bo、Abdullahi Adam、Ferreira Isabella A. T. M.、Goonawardane Niluka、Saito Akatsuki、Kimura Izumi、Yamasoba Daichi、Other 48 authors、Sato Kei、Gupta Ravindra K.
  • Journal Title: Nature Volume: 603 Pages: 706-714
  • DOI: 10.1038/s41586-022-04474-x
  • 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 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 Pages: 0-0
  • DOI: 10.1093/infdis/jiac053
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Sarbecovirus ORF6 proteins hamper the induction of interferon signaling (2021)
  • Author(s): Kimura I, Konno Y, Uriu K, Hopfensperge K, Sauter D, Nakagawa S, Sato K
  • Journal Title: Cell Reports Volume: 34 Pages: 108916-108916
  • DOI: 10.1016/j.celrep.2021.108916
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A comprehensive investigation on the interplay between feline APOBEC3Z3 proteins and feline immunodeficiency virus Vif proteins. Journal of Virology. (2021)
  • Author(s): Yusuke Kosugi‡, Keiya Uriu‡, Narumi Suzuki‡, Keisuke Yamamoto‡, Shumpei Nagaoka‡, Izumi Kimura‡, Yoriyuki Konno‡, Hirofumi Aso‡, Brian J Willett, Tomoko Kobayashi, Yoshio Koyanagi, Mahoko Takahashi Ueda, Jumpei Ito and Kei Sato. ‡Equal contribution.
  • Journal Title: Journal of Virology Volume: 00178-21 Pages: 0-0
  • DOI: 10.1128/jvi.00178-21
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Elucidation of the Complicated Scenario of Primate APOBEC3 Gene Evolution (2021)
  • Author(s): Uriu Keiya、Kosugi Yusuke、Suzuki Narumi、Ito Jumpei、Sato Kei
  • Journal Title: Journal of Virology Volume: 95 Pages: 0-0
  • DOI: 10.1128/jvi.00144-21
  • Peer Reviewed / Open Access
• [Journal Article] SARS-CoV-2 spike L452R variant evades cellular immunity and increases infectivity (2021)
  • Author(s): Motozono Chihiro、Toyoda Mako、Zahradnik Jiri、Saito Akatsuki、Other 19 authors、Ikeda Terumasa、Nakagawa So、Ueno Takamasa、Sato Kei
  • Journal Title: Cell Host & Microbe Volume: 29 Pages: 1124-1136
  • DOI: 10.1016/j.chom.2021.06.006
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] SARS-CoV-2 B.1.617 Mutations L452R and E484Q Are Not Synergistic for Antibody Evasion (2021)
  • Author(s): Ferreira IATM, Kemp SA, Datir R, Saito A, Meng B, Rakshit P, Takaori-Kondo A, Kosugi Y, Uriu K, Kimura I, Shirakawa K, Abdullahi A, Agarwal A, Ozono S, Tokunaga K, Sato K, Gupta RK
  • Journal Title: The Journal of Infectious Diseases Volume: 224 Pages: 989-994
  • DOI: 10.1093/infdis/jiab368
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] IFITM proteins promote SARS-CoV-2 infection and are targets for virus inhibition in vitro (2021)
  • Author(s): Prelli Bozzo Caterina et al.
  • Journal Title: Nature Communications Volume: 12 Pages: 0-0
  • DOI: 10.1038/s41467-021-24817-y
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion (2021)
  • Author(s): Mlcochova Petra、Kemp Steven A.、Dhar Mahesh Shanker他
  • Journal Title: Nature Volume: 599 Pages: 114-119
  • DOI: 10.1038/s41586-021-03944-y
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] An additional NF-κB site allows HIV-1 subtype C to evade restriction by nuclear PYHIN proteins (2021)
  • Author(s): Bosso Matteo、Sturzel Christina M.、Kmiec Dorota、Badarinarayan Smitha Srinivasachar、Braun Elisabeth、Ito Jumpei、Sato Kei、Hahn Beatrice H.、Sparrer Konstantin M.J.、Sauter Daniel、Kirchhoff Frank
  • Journal Title: Cell Reports Volume: 36 Pages: 109735-109735
  • DOI: 10.1016/j.celrep.2021.109735
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Neutralization of the SARS-CoV-2 Mu Variant by Convalescent and Vaccine Serum (2021)
  • Author(s): Uriu Keiya、Kimura Izumi、Shirakawa Kotaro、Takaori-Kondo Akifumi、Nakada Taka-aki、Kaneda Atsushi、Nakagawa So、Sato Kei
  • Journal Title: New England Journal of Medicine Volume: 385 Pages: 2397-2399
  • DOI: 10.1056/nejmc2114706
  • 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 Pages: 300-306
  • DOI: 10.1038/s41586-021-04266-9
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Evolutionary plasticity of SH3 domain binding by Nef proteins of the HIV-1/SIVcpz lentiviral lineage (2021)
  • Author(s): Zhao Zhe、Fagerlund Riku、Tossavainen Helena、Hopfensperger Kristina、Lotke Rishikesh、Srinivasachar Badarinarayan Smitha、Kirchhoff Frank、Permi Perttu、Sato Kei、Sauter Daniel、Saksela Kalle
  • Journal Title: PLOS Pathogens Volume: 17 Pages: 0-0
  • DOI: 10.1371/journal.ppat.1009728
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The True Nature of Viruses Elucidated by Systems Virology (2021)
  • Author(s): Sato Kei
  • Journal Title: Frontiers in Virology Volume: 1 Pages: 0-0
  • DOI: 10.3389/fviro.2021.808865
  • Peer Reviewed / Open Access
• [Journal Article] HIV-1 tracing method of systemic viremia in vivo using an artificially mutated virus pool (2021)
  • Author(s): Andrew Soper, Yoshio Koyanagi, Kei Sato
  • Journal Title: Microbiology and Immunology Volume: 65 Pages: 17-27
  • DOI: 10.1111/1348-0421.12862
  • Peer Reviewed
• [Journal Article] Direct evidence of abortive lytic infection-mediated establishment of Epstein-Barr virus latency during B-cell infection (2021)
  • Author(s): Inagaki T, Sato Y, Ito J, Takaki M, Okuno Y, Yaguchi M, Masud MHAA, Watanabe T, Sato K, Iwami S, MurataT, Kimura H
  • Journal Title: Frontiers in Microbiology, 11:575255 (2021). Volume: 11 Pages: 575255-575255
  • DOI: 10.3389/fmicb.2020.575255
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Retroviruses drive the rapid evolution of mammalian APOBEC3 genes (2020)
  • Author(s): Jumpei Ito, Robert J. Gifford, Kei Sato
  • Journal Title: Proceedings of the National Academy of Sciences Volume: 117 Pages: 610-618
  • DOI: 10.1073/pnas.1914183116
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Inherited chromosomally integrated HHV-6 possibly modulates human gene expression (2020)
  • Author(s): Kumata Ryuichi、Ito Jumpei、Sato Kei
  • Journal Title: Virus Genes Volume: 56 Pages: 386-389
  • DOI: 10.1007/s11262-020-01745-5
  • Peer Reviewed
• [Journal Article] Quantifying the antiviral effect of APOBEC3 on HIV-1 infection in humanized mouse model (2020)
  • Author(s): Tatsuya Kurusu, Kwang Su Kim, Yoshiki Koizumi, Shinji Nakaoka, Keisuke Ejima, Naoko Misawa, Yoshio Koyanagi, Kei Sato, Shingo Iwami
  • Journal Title: Journal of Theoretical Biology Volume: 498 Pages: 110295-110295
  • DOI: 10.1016/j.jtbi.2020.110295
  • Peer Reviewed
• [Journal Article] A tissue level atlas of the healthy human virome (2020)
  • Author(s): Kumata Ryuichi、Ito Jumpei、Takahashi Kenta、Suzuki Tadaki、Sato Kei
  • Journal Title: BMC Biology Volume: 18 Pages: 1-15
  • DOI: 10.1186/s12915-020-00785-5
  • Peer Reviewed / Open Access
• [Journal Article] Multiomics Investigation Revealing the Characteristics of HIV-1-Infected Cells In Vivo (2020)
  • Author(s): Hirofumi Aso, Shumpei Nagaoka, Eiryo Kawakami, Jumpei Ito, Saiful Islam, Benjy Jek Yang Tan, Shinji Nakaoka, Koichi Ashizaki, Katsuyuki Shiroguchi, Yutaka Suzuki, Yorifumi Satou, Yoshio Koyanagi, Kei Sato
  • Journal Title: Cell Reports Volume: 32 Pages: 107887-107887
  • DOI: 10.1016/j.celrep.2020.107887
  • Peer Reviewed / Open Access
• [Journal Article] Endogenization and excision of human herpesvirus 6 in human genomes. (2020)
  • Author(s): Xiaoxi Liu, Shunichi Kosugi, Rie Koide, Yoshiki Kawamura, Jumpei Ito, Hiroki Miura, Nana Matoba, Motomichi Matsuzaki , and other 14 authors
  • Journal Title: PLOS Genetics Volume: 16 Pages: 1008915-1008915
  • DOI: 10.1371/journal.pgen.1008915
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Phosphoregulation of a Conserved Herpesvirus Tegument Protein by a Virally Encoded Protein Kinase in Viral Pathogenicity and Potential Linkage between Its Evolution and Viral Phylogeny (2020)
  • Author(s): Shibazaki Misato、Kato Akihisa、Takeshima Kosuke、Ito Jumpei、Suganami Mai、Koyanagi Naoto、Maruzuru Yuhei、Sato Kei、Kawaguchi Yasushi
  • Journal Title: J. Virol. Volume: 94 Pages: 1055-1055
  • DOI: 10.1128/jvi.01055-20
  • Peer Reviewed / Open Access
• [Journal Article] A role for gorilla APOBEC3G in shaping lentivirus evolution including transmission to humans (2020)
  • Author(s): Nakano Yusuke、Yamamoto Keisuke、Ueda Mahoko Takahashi、Soper Andrew、Konno Yoriyuki、Kimura Izumi、Uriu Keiya、Kumata Ryuichi、Aso Hirofumi、Misawa Naoko、Nagaoka Shumpei、Shimizu Soma、Mitsumune Keito、Kosugi Yusuke、Juarez-Fernandez Guillermo、Ito Jumpei、...、Koyanagi Yoshio、Harris Reuben S.、Sato Kei
  • Journal Title: PLOS Pathogens Volume: 16 Pages: 1008812-1008812
  • DOI: 10.1371/journal.ppat.1008812
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] SARS-CoV-2 ORF3b Is a Potent Interferon Antagonist Whose Activity Is Increased by a Naturally Occurring Elongation Variant (2020)
  • Author(s): Konno Yoriyuki、Kimura Izumi、Uriu Keiya、Fukushi Masaya、Irie Takashi、Koyanagi Yoshio、Sauter Daniel、Gifford Robert J.、Nakagawa So、Sato Kei
  • Journal Title: Cell Rep Volume: 32 Pages: 108185-108185
  • DOI: 10.1016/j.celrep.2020.108185
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Endogenous retroviruses drive KRAB zinc-finger protein family expression for tumor suppression (2020)
  • Author(s): Ito Jumpei、Kimura Izumi、Soper Andrew、Coudray Alexandre、Koyanagi Yoshio、Nakaoka Hirofumi、Inoue Ituro、Turelli Priscilla、Trono Didier、Sato Kei
  • Journal Title: Science Advances Volume: 6 Pages: 3020-3020
  • DOI: 10.1126/sciadv.abc3020
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Reconstitution of prospermatogonial specification in vitro from human induced pluripotent stem cells (2020)
  • Author(s): Hwang Young Sun、Suzuki Shinnosuke、Seita Yasunari、Ito Jumpei、Sakata Yuka、Aso Hirofumi、Sato Kei、Hermann Brian P.、Sasaki Kotaro
  • Journal Title: Nature Communications Volume: 11 Pages: 5656-5656
  • DOI: 10.1038/s41467-020-19350-3
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The significance of disseminated intravascular coagulation on multiple organ dysfunction during the early stage of acute respiratory distress syndrome (2020)
  • Author(s): Gando S、Fujishima S、Saitoh D、Shiraishi A、Yamakawa K、Kushimoto S、Ogura H、Abe T、et al
  • Journal Title: QJM: An International Journal of Medicine Volume: 191 Pages: 15-21
  • DOI: 10.1093/qjmed/hcaa296
  • Peer Reviewed / Open Access
• [Journal Article] Comparative description of the expression profile of interferon-stimulated genes in multiple cell lineages targeted by HIV-1 infection (2019)
  • Author(s): Hirofumi Aso, Jumpei Ito, Yoshio Koyanagi & Kei Sato
  • Journal Title: Frontiers in Microbiology Volume: 10 Pages: 429-429
  • DOI: 10.3389/fmicb.2019.00429
  • Peer Reviewed / Open Access
• [Journal Article] N4BP1 restricts HIV-1 and its inactivation by MALT1 promotes viral reactivation. (2019)
  • Author(s): Yamasoba D, Sato K, Ichinose T, Imamura T, Koepke L, Joas S, Reith E, Hotter D, Misawa N, Akaki K, Uehata T, Mino T, Miyamoto S, Noda T, Yamashita A, Standley DM, Kirchhoff F, Sauter D, Koyanagi Y, Takeuchi O.
  • Journal Title: Nat Microbiol. Volume: 4 Pages: 1532-1544
  • DOI: 10.1038/s41564-019-0460-3
  • NAID: 120006731123
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] New World feline APOBEC3 potently controls inter-genus lentiviral transmission (2018)
  • Author(s): Yoriyuki Konno, Shumpei Nagaoka, Izumi Kimura, Keisuke Yamamoto, Yumiko Kagawa, Ryuichi Kumata, Hirofumi Aso, Mahoko Takahashi Ueda, So Nakagawa, Tomoko Kobayashi, Yoshio Koyanagi, Kei Sato
  • Journal Title: Rerovirology Volume: 15 Pages: 31-31
  • DOI: 10.1186/s12977-018-0414-5
  • Peer Reviewed / Open Access
• [Presentation] Human-specific adaptations in Vpu conferring anti-tetherin activity are critical for efficient early HIV-1 replication in vivo (2019)
  • Author(s): Kei Sato
  • Organizer: Highlights in Basic andClinical Research in HIV/AIDS
  • Int'l Joint Research / Invited
• [Book] ネオウイルス学 (2021)
  • Author(s): 河岡 義裕、岩見 真吾、大場 靖子、川口 寧、佐藤 佳、澤 洋文、鈴木 信弘、高橋 英樹、朝長 啓造、中川 草、長崎 慶三、西浦 博、野田 岳志、古瀬 祐気、堀江 真行、牧野 晶子、松浦 善治、松野 啓太、村田 和義、望月 智弘、渡辺 登喜子
  • Total Pages: 320
  • Publisher: 集英社
  • ISBN: 4087211592