Investigation of the molecular mechanism of AIDS virus evolution

• Project/Area Number: 15K07166
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Evolutionary biology
• Research Institution: Kyoto University
• Principal Investigator: Sato Kei 京都大学, ウイルス・再生医科学研究所, 講師 (10593684)
• Co-Investigator(Renkei-kenkyūsha): Koyanagi Yoshio 京都大学・ウイルス, 再生医科学研究所, 教授 (80215417) ; Iwasa You 九州大学, 理学研究院, 教授 (70176535) ; Iwami Shingo 九州大学, 理学研究院, 准教授 (90518119) ; Ren FengRong 東京医科歯科大学, 難治疾患研究所, 特任准教授 (60280989) ; Nakagawa So 東海大学, 医学部, 講師 (70510014)
• Research Collaborator: Dong Sung An カリフォルニア大学ロサンゼルス校, 教授
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: システムウイルス学 / HIV-1 / チンパンジー / ヒト化マウス / 適応進化 / HIV / SIV / 進化ウイルス学 / エイズ

Outline of Final Research Achievements

HIV-1, the causative agent of AIDS, is originated from SIVcpz, the chimpanzee precursor of the human virus, approximately 100 years ago. This indicates that HIV-1 has emerged through the cross-species transmission of SIVcpz from chimpanzees to humans. However, it remains unclear how SIVcpz has evolved into pandemic HIV-1 in humans. To address this question, we used three SIVcpz (MB897, EK505, and MT145), four pandemic HIV-1 (NL4-3, NLCSFV3, JRCSF and AD8) and 2 non-pandemic HIV-1 (YBF30 and DJO0131) strains and humanized mouse model. This is the first experimental investigation to use an animal model to demonstrate a gain-of-function evolution of SIVcpz into pandemic HIV-1.

Research Products

• [Journal Article] Type I interferon responses by HIV-1 infection: association with disease progression and control (2018)
  • Author(s): Andrew Soper, Izumi Kimura, Shumpei Nagaoka, Yoriyuki Konno, Keisuke Yamamoto, Yoshio Koyanagi & Kei Sato*. (*Correspondence)
  • Journal Title: Frontiers in Immunology Volume: 8 Pages: 1823-1823
  • DOI: 10.3389/fimmu.2017.01823
  • Peer Reviewed / Open Access
• [Journal Article] Experimental adaptive evolution of simian immunodeficiency virus SIVcpz to pandemic human immunodeficiency virus type 1 using a humanized mouse model (2018)
  • Author(s): Kei Sato*, Naoko Misawa, Junko S Takeuchi, Tomoko Kobayashi, Taisuke Izumi, Hirofumi Aso, Shumpei Nagaoka, Keisuke Yamamoto, Izumi Kimura, Yoriyuki Konno, Yusuke Nakano & Yoshio Koyanagi. (*Correspondence)
  • Journal Title: Journal of Virology Volume: 92 Issue: 4
  • DOI: 10.1128/jvi.01905-17
  • Peer Reviewed
• [Journal Article] Different effects of two mutations on the infectivity of Ebola virus glycoprotein in nine mammalian species (2018)
  • Author(s): Kurosaki, Y., Ueda, M.T., Nakano, Y., Yasuda, J., Koyanagi, Y., Sato, K. and Nakagawa, S.
  • Journal Title: Journal of General Virology Volume: 99(2) Issue: 2 Pages: 181-186
  • DOI: 10.1099/jgv.0.000999
  • Peer Reviewed / Open Access
• [Journal Article] HIV-1 competition experiments in humanized mice show that APOBEC3H imposes selective pressure and promotes virus adaptation. (2017)
  • Author(s): Yusuke Nakano, Naoko Misawa, Guillermo Juarez-Fernandez, Miyu Moriwaki, Shinji Nakaoka, Takaaki Funo, Eri Yamada, Andrew Soper, Rokusuke Yoshikawa, Diako Ebrahimi, Yuuya Tachiki, Shingo Iwami, Reuben S. Harris, Yoshio Koyanagi & Kei Sato
  • Journal Title: PLOS Pathogens Volume: 13 Issue: 5 Pages: 31-31
  • DOI: 10.1371/journal.ppat.1006348
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Human-specific adaptations in Vpu conferring anti-tetherin activity are critical for efficient early HIV-1 replication in vivo. (2017)
  • Author(s): Eri Yamada, Shinji Nakaoka, Lukas Klein, Elisabeth Reith, Simon Langer, Kristina Hopfensperger, Shingo Iwami, Gideon Schreiber, Frank Kirchhoff, Yoshio Koyanagi, Daniel Sauter & Kei Sato
  • Journal Title: Cell Host & Microbe Volume: 23 Issue: 1 Pages: 110-120
  • DOI: 10.1016/j.chom.2017.12.009
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Quantifying the effect of Vpu on the promotion of HIV-1 replication in the humanized mouse model (2016)
  • Author(s): Ikeda H, Nakaoka S, de Boer RJ, Morita S, Misawa N, Koyanagi Y, Aihara K, Sato K, Iwami S
  • Journal Title: Retrovirology Volume: 13 Issue: 1 Pages: 23-23
  • DOI: 10.1186/s12977-016-0252-2
  • NAID: 120006353849
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Modelling Ebola virus dynamics: Implications for therapy. (2016)
  • Author(s): Martyushev A, Nakaoka S, Sato K, Noda T, Iwami S.
  • Journal Title: Antiviral Res Volume: 135 Pages: 62-73
  • DOI: 10.1016/j.antiviral.2016.10.004
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] A naturally occurring bovine APOBEC3 confers resistance to bovine lentiviruses: implication for the co-evolution of bovids and their lentiviruses. (2016)
  • Author(s): Yamada E, Yoshikawa R, Nakano Y, Misawa N, Kobayashi T, Ren F, Izumi T, Miyazawa T, Koyanagi Y, Sato K.
  • Journal Title: Sci Rep Volume: 6:33988 Issue: 1 Pages: 33988-33988
  • DOI: 10.1038/srep33988
  • NAID: 120005997850
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Small ruminant lentiviral Vif proteins commonly utilize cyclophilin A, an evolutionary and structurally conserved protein, to degrade ovine and caprine APOBEC3 proteins (2016)
  • Author(s): Yoshikawa R, Izumi T, Nakano Y, Yamada E, Moriwaki M, Misawa N, Ren F, Kobayashi T, Koyanagi Y, Sato K.
  • Journal Title: Microbiol Immunol Volume: 60 Issue: 6 Pages: 427-436
  • DOI: 10.1111/1348-0421.12387
  • Peer Reviewed / Open Access
• [Journal Article] A naturally occurring domestic cat APOBEC3 variant confers resistance to FIV infection (2016)
  • Author(s): Rokusuke Yoshikawa, Taisuke Izumi, Eri Yamada, Yusuke Nakano, Naoko Misawa, Fengrong Ren, Michael A. Carpenter, Terumasa Ikeda, Carsten Münk, Reuben S. Harris, Takayuki Miyazawa, Yoshio Koyanagi & Kei Sato
  • Journal Title: Journal of Virology Volume: 90 Issue: 1 Pages: 474-485
  • DOI: 10.1128/jvi.02612-15
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Species-specific differences in the ability of feline lentiviral Vif to degrade feline APOBEC3 proteins. (2016)
  • Author(s): Yoshikawa R, Nakano Y, Yamada E, Izumi T, Misawa N, Koyanagi Y, Sato K.
  • Journal Title: Microbiol Immunol Volume: 60 Issue: 4 Pages: 272-279
  • DOI: 10.1111/1348-0421.12371
  • NAID: 40020808948
  • Peer Reviewed / Open Access
• [Journal Article] Determinants of FIV and HIV Vif sensitivity of feline APOBEC3 restriction factors (2016)
  • Author(s): Zhang Z, Gu Q, Jaguva Vasudevan AA, Hain A, Kloke BP, Hasheminasab S, Mulnaes D, Sato K, Cichutek K, Haussinger D, Bravo IG, Smits SH, Gohlke H, Munk C
  • Journal Title: Retrovirology Volume: 13 Issue: 1 Pages: 46-46
  • DOI: 10.1186/s12977-016-0274-9
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] APOBEC3 proteins can copackage and comutate HIV-1 genomes. (2016)
  • Author(s): Desimmie BA, Burdick RC, Izumi T, Doi H, Shao W, Alvord WG, Sato K, Koyanagi Y, Jones S, Wilson E, Hill S, Maldarelli F, Hu WS, Pathak VK.
  • Journal Title: Nucleic Acids Res Volume: 44: Issue: 16 Pages: 7848-7865
  • DOI: 10.1093/nar/gkw653
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Dynamics of HIV infection in lymphoid tissue network (2015)
  • Author(s): Shinji Nakaoka, Shingo Iwami & Kei Sato
  • Journal Title: Journal of Mathematical Biology Volume: 72 Issue: 4 Pages: 909-938
  • DOI: 10.1007/s00285-015-0940-x
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Pandemic HIV-1 Vpu overcomes intrinsic herd immunity mediated by tetherin (2015)
  • Author(s): Shingo Iwami, Kei Sato, Satoru Morita, Hisashi Inaba, Tomoko Kobayashi, Junko S. Takeuchi, Yuichi Kimura, Naoko Misawa, Fengrong Ren, Yoh Iwasa, Kazuyuki Aihara & Yoshio Koyanagi
  • Journal Title: Scientific Reports Volume: 5 Issue: 1 Pages: 12256-12256
  • DOI: 10.1038/srep12256
  • NAID: 120005774579
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Down-modulation of primate lentiviral receptors by Nef proteins of simian immunodeficiency virus (SIV) of chimpanzees (SIVcpz) and related SIVs: implication for the evolutionary event at the emergence of SIVcpz (2015)
  • Author(s): Yusuke Nakano, Kenta Matsuda, Rokusuke Yoshikawa, Eri Yamada, Naoko Misawa, Vanessa M. Hirsch, Yoshio Koyanagi & Kei Sato
  • Journal Title: Journal of General Virology Volume: 96 Issue: 9 Pages: 2867-2877
  • DOI: 10.1099/vir.0.000207
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Cell-to-cell infection by HIV contributes over half of virus infection (2015)
  • Author(s): Shingo Iwami, Junko S. Takeuchi, Shinji Nakaoka, Fabrizio Mammano, François Clavel, Hisashi Inaba, Tomoko Kobayashi, Naoko Misawa, Kazuyuki Aihara, Yoshio Koyanagi & Kei Sato
  • Journal Title: eLife Volume: 4 Pages: 1-16
  • DOI: 10.7554/elife.08150
  • NAID: 120005997708
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Coevolutionary dynamics between tribe Cercopithecini tetherins and their lentiviruses (2015)
  • Author(s): Junko S. Takeuchi, Fengrong Ren, Rokusuke Yoshikawa, Eri Yamada, Yusuke Nakano, Tomoko Kobayashi, Kenta Matsuda, Taisuke Izumi, Naoko Misawa, Yuta Shintaku, Katherine S. Wetzel, Ronald G. Collman, Hiroshi Tanaka, Vanessa M. Hirsch, Yoshio Koyanagi & Kei Sato
  • Journal Title: Scientific Reports Volume: 5 Issue: 1 Pages: 16021-16021
  • DOI: 10.1038/srep16021
  • NAID: 120005753887
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Experimental evaluation of the zoonotic infection potency of simian retrovirus type 4 using humanized mouse model (2015)
  • Author(s): Kei Sato, Tomoko Kobayashi, Naoko Misawa, Rokusuke Yoshikawa, Junko S. Takeuchi, Tomoyuki Miura, Munehiro Okamoto, Jun-ichirou Yasunaga, Masao Matsuoka, Mamoru Ito, Takayuki Miyazawa & Yoshio Koyanagi
  • Journal Title: Scientific Reports Volume: 5 Issue: 1 Pages: 14040-14040
  • DOI: 10.1038/srep14040
  • NAID: 120005753867
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A conservation law for virus infection kinetics in vitro (2015)
  • Author(s): Yusuke Kakizoe, Satoru Morita, Shinji Nakaoka, Yasuhiro Takeuchi, Kei Sato, Tomoyuki Miura, Catherine A. A. Beauchemin, and Shingo Iwami
  • Journal Title: Journal of Theoretical Biology Volume: 376 Pages: 39-47
  • DOI: 10.1016/j.jtbi.2015.03.034
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Impacts of humanized mouse models on the investigation of HIV-1 infection: illuminating the roles of viral accessory proteins in vivo. (2015)
  • Author(s): Yamada, E., Yoshikawa, R., Nakano, Y., Misawa, N., Koyanagi, Y., Sato, K.
  • Journal Title: Viruses Volume: 7 Issue: 3 Pages: 1373-1390
  • DOI: 10.3390/v7031373
  • NAID: 120005774663
  • Peer Reviewed / Open Access
• [Journal Article] Vif determines the requirement for CBF-β in APOBEC3 degradation (2015)
  • Author(s): Rokusuke Yoshikawa, Junko S. Takeuchi, Eri Yamada, Yusuke Nakano, Fengrong Ren, Hiroshi Tanaka, Carsten Münk, Reuben S. Harris, Takayuki Miyazawa, Yoshio Koyanagi & Kei Sato
  • Journal Title: Journal of General Virology Volume: 86 Issue: 4 Pages: 887-892
  • DOI: 10.1099/jgv.0.000027
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Gain-of-function evolution of SIVcpz in humanized mouse model (2016)
  • Author(s): Sato, K., Misawa, N., Takeuchi, J.S., Kobayashi, T., Yamada, E., Nakano, Y., Yoshikawa, R. and Koyanagi, Y
  • Organizer: Cold Spring Harbor Retrovirus meeting
  • Place of Presentation: New York, USA
  • Int'l Joint Research
• [Presentation] Investigation of the interplay between cellular proteins and HIV-1-encoding proteins using humanized mouse model (2016)
  • Author(s): Sato, K
  • Organizer: The 15th Awaji International Forum on Infection and Immunity
  • Place of Presentation: 淡路島
  • Int'l Joint Research / Invited
• [Presentation] エボラウィルス糖蛋白質（GP）遺伝子の分子進化解析 (2015)
  • Author(s): 上田真保子、泉泰輔、佐藤佳、中川草
  • Organizer: BMB2015
  • Place of Presentation: 神戸
  • Year and Date: 2015-12-03
• [Presentation] ウシ族の進化過程におけるAPOBEC3Z2蛋白質の発現レベル多様性の出現 (2015)
  • Author(s): 中野雄介、山田英里、吉川禄助、泉泰輔、小林朋子、三沢尚子、任鳳蓉、佐藤佳、小柳義夫
  • Organizer: BMB2015
  • Place of Presentation: 神戸
  • Year and Date: 2015-12-03
• [Presentation] Impact of genetic and functional changes in HIV-1 and SIVcpz transmission (2015)
  • Author(s): Sato, K. and Koyanagi, Y
  • Organizer: 第29回日本エイズ学会学術集会・総会
  • Place of Presentation: 東京
  • Year and Date: 2015-11-30
• [Presentation] Evolutionary arms race between viruses and mammals: an interdisciplinary research of experimental virology and molecular phylogenetic (2015)
  • Author(s): Sato, K
  • Organizer: 日本バイオインフォマティクス学会生命システム理論研究会
  • Place of Presentation: 東京
  • Year and Date: 2015-11-27
  • Invited
• [Presentation] Dynamics of HIV-1 infection in humanized mouse model (2015)
  • Author(s): Sato, K
  • Organizer: 第63回日本ウイルス学会学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2015-11-24
  • Invited
• [Presentation] Evolutionary arms race between domestic cat (Felis catus) and its cognate lentivirus (FIV) (2015)
  • Author(s): Yoshikawa, R., T. Izumi, Yamada, E., Nakano, Y., Misawa, N., Ren, F., Miyazawa, T., Sato, K., and Koyanagi, Y
  • Organizer: 第63回日本ウイルス学会学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2015-11-22
• [Presentation] Functional positive selection of a bovine APOBEC3 driven by bovine lentivirus (2015)
  • Author(s): Yamada, E., Yoshikawa, R., T. Izumi, Nakano, Y., Misawa, N., Kobayashi, T., Ren, F., Sato, K., and Koyanagi, Y
  • Organizer: 第63回日本ウイルス学会学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2015-11-22
• [Presentation] Evolutionary dynamics of HIV-1-lineage lentiviruses and primates: evolutionary arms race between viral protein and host protein (2015)
  • Author(s): Sato, K
  • Organizer: Innovative Mathematical Modeling for the Analysis of Infectious Disease Data
  • Place of Presentation: 札幌
  • Year and Date: 2015-10-30
  • Int'l Joint Research
• [Presentation] 自然発生Vif変異によるレンチウイルスの弱毒化 (2015)
  • Author(s): 吉川禄助、竹内(柴田)潤子、山田英里、中野雄介、木村雄一、橋本暁、宮沢孝幸、佐藤佳、小柳義夫
  • Organizer: 第158回日本獣医学会
  • Place of Presentation: 十和田
  • Year and Date: 2015-09-07
• [Presentation] 動物レンチウイルスからみるウイルスと宿主の共進化 (2015)
  • Author(s): 吉川禄助, 泉泰輔, 山田英里, 中野雄介, 任鳳蓉, 宮沢孝幸, 佐藤佳, 小柳義夫
  • Organizer: 第17回日本進化学会
  • Place of Presentation: 東京
  • Year and Date: 2015-08-20
• [Presentation] ネコAPOBEC3Z3多型とFIV感染感受性との関係性 (2015)
  • Author(s): 吉川禄助, 泉泰輔, 山田英里, 中野雄介, 任鳳蓉, 宮沢孝幸, 佐藤佳, 小柳義夫
  • Organizer: 第21回野生動物医学会
  • Place of Presentation: 江別
  • Year and Date: 2015-08-01
• [Presentation] ウシ族の進化とレンチウイルスの関連についての考察 (2015)
  • Author(s): 山田英里, 中野雄介, 吉川禄助, 泉泰輔, 小林朋子，任鳳蓉, 宮沢孝幸, 小柳義夫, 佐藤佳
  • Organizer: 第21回野生動物医学会
  • Place of Presentation: 江別
  • Year and Date: 2015-08-01
• [Presentation] チンパンジーからのエイズウイルス適応原理の解析 (2015)
  • Author(s): 佐藤佳
  • Organizer: 第17回白馬シンポジウム
  • Place of Presentation: 米子
  • Year and Date: 2015-06-19
  • Invited
• [Presentation] A naturally occurring domestic cat APOBEC3 variant confers resistance to FIV infection (2015)
  • Author(s): Yoshikawa, R., T. Izumi, Yamada, E., Nakano, Y., Misawa, N., Ren, F., Carpenter, M. A., Ikeda, T., Münk, C., Harris, R. S., Miyazawa, T., Sato, K., and Koyanagi, Y
  • Organizer: Cold Spring Harbor Laboratory Meeting on Retroviruses
  • Place of Presentation: New York
  • Year and Date: 2015-05-22
  • Int'l Joint Research
• [Presentation] Experimental adaptive evolution of SIVcpz to humans using humanized mouse model (2015)
  • Author(s): Sato, K., Misawa, N., Takeuchi, J. S., Kobayashi, T., Yamada, E., Nakano, Y., Yoshikawa, R., and Koyanagi, Y
  • Organizer: Cold Spring Harbor Laboratory Meeting on Retroviruses
  • Place of Presentation: New York
  • Year and Date: 2015-05-21
  • Int'l Joint Research