Human norovirus

• Project/Area Number: 19K22532
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 49:Pathology, infection/immunology, and related fields
• Research Institution: Osaka University
• Principal Investigator: Sato Shintaro 大阪大学, 微生物病研究所, 特任准教授(常勤) (80447333)
• Project Period (FY): 2019-06-28 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000); Fiscal Year 2020: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2019: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: ヒトノロウイルス / 受容体

Outline of Research at the Start

本研究計画の目的は、ヒトノロウイルス（HuNoV）の侵入に関与する宿主側のタンパク質レセプターの同定を目的とし、さらにその分子を発現する一般的な細胞株やトランスジェニックマウスを作出することで、HuNoVに対するワクチン開発に資する、改良型in vitro HuNoV増殖系の確立、および、HuNoV感染モデルマウスの作製を目指す。

Outline of Final Research Achievements

In order to screen for human norovirus receptors using the CRISPR/Cas9 system, we searched for human norovirus lots that have a cytopathic effect, however, no cytopathic effect was observed even when the virus concentration was increased 100 times. Five genes that may be involved in human norovirus infection and proliferation were determined. Each was forcibly expressed using a lentiviral vector in epithelial cells showing no propagation of human norovirus. We are currently investigating the ability of these cells to proliferate human norovirus.

Academic Significance and Societal Importance of the Research Achievements

ヒトノロウイルスのin vitro増殖が可能になってからすでに5年近く経過したが、その増殖系を用いたヒトノロウイルスの性状解析などは未だに進んでおらず、申請者らも挑戦しているが、細胞変性効果を示す実験系も確立されていない。今後も地道に解析を継続することで、ヒトノロウイルスに対するワクチン、治療薬の開発に繋がるものと思われる。

Research Products

• [Journal Article] Development of Antibody-Fragment?Producing Rice for Neutralization of Human Norovirus (2021)
  • Author(s): Sasou Ai、Yuki Yoshikazu、Kurokawa Shiho、Sato Shintaro、Goda Yuki、Uchida Masao、Matsumoto Naomi、Sagara Hiroshi、Watanabe Yuji、Kuroda Masaharu、Sakon Naomi、Sugiura Kotomi、Nakahashi-Ouchida Rika、Ushijima Hiroshi、Fujihashi Kohtaro、Kiyono Hiroshi
  • Journal Title: Frontiers in Plant Science Volume: 12 Pages: 639953-639953
  • DOI: 10.3389/fpls.2021.639953
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Alcohol abrogates human norovirus infectivity in a pH-dependent manner (2020)
  • Author(s): Sato Shintaro、Matsumoto Naomi、Hisaie Kota、Uematsu Satoshi
  • Journal Title: Scientific Reports Volume: 10 Issue: 1 Pages: 15878-15878
  • DOI: 10.1038/s41598-020-72609-z
  • NAID: 120006891639
  • Peer Reviewed / Open Access
• [Journal Article] Metagenome Data on Intestinal Phage-Bacteria Associations Aids the Development of Phage Therapy against Pathobionts (2020)
  • Author(s): Fujimoto Kosuke、Kimura Yasumasa、Shimohigoshi Masaki、Satoh Takeshi、Sato Shintaro、Tremmel Georg、Uematsu Miho、Kawaguchi Yunosuke、Usui Yuki、Nakano Yoshiko、Hayashi Tetsuya、Kashima Koji、Yuki Yoshikazu、Yamaguchi Kiyoshi、Furukawa Yoichi、Kakuta Masanori、Akiyama Yutaka、Yamaguchi Rui、Crowe Sheila E. et al
  • Journal Title: Cell Host & Microbe Volume: 28 Issue: 3 Pages: 380-389
  • DOI: 10.1016/j.chom.2020.06.005
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A heterodimeric antibody fragment for passive immunotherapy against norovirus infection (2020)
  • Author(s): Yuki Yoshikazu、Kurokawa Shiho、Sato Shintaro、Sasou Ai、Matsumoto Naomi、Suzuki Akio、Sakon Naomi、Goda Yuki、Takeyama Natsumi、Miyoshi Tatsuya、Marcotte Harold、Tanaka Tomoyuki、Hammarstrom Lennart、Kiyono Hiroshi
  • Journal Title: The Journal of Infectious Diseases Volume: － Issue: 3 Pages: 470-478
  • DOI: 10.1093/infdis/jiaa115
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Osteoprotegerin-dependent Mcell self-regulation balances gut infection and immunity. (2020)
  • Author(s): Kimura S, Nakamura Y, Kobayashi N, Shiroguchi K, KawakamiE, Mutoh M, Takahashi-Iwanaga H, Yamada T, Hisamoto M, Nakamura M, Udagawa N, Sato S, KaishoT, Iwanaga T, Hase K.
  • Journal Title: Nat Commun Volume: 11 Issue: 1 Pages: 234-234
  • DOI: 10.1038/s41467-019-13883-y
  • Peer Reviewed / Open Access
• [Journal Article] Persistent colonization of non-lymphoid tissue-resident macrophages by Stenotrophomonas maltophilia (2019)
  • Author(s): Takahashi Ichiro, Hosomi Koji, Nagatake Takahiro, Tobou Hirokazu, Yamamoto Daiki, Hayashi Ikue, Kurashima Yosuke, Sato Shintaro, Shibata Naoko, Goto Yoshiyuki, Maruyama Fumito, Nakagawa Ichiro, Kuwae Asaomi, Abe Akio, Kunisawa Jun, Kiyono Hiroshi
  • Journal Title: International Immunology Volume: 32 Issue: 2 Pages: 133-141
  • DOI: 10.1093/intimm/dxz071
  • NAID: 120006888456
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A role for the CCR5?CCL5 interaction in the preferential migration of HSV-2-specific effector cells to the vaginal mucosa upon nasal immunization (2019)
  • Author(s): Joo Sunyi、Suwanto Aldina、Sato Ayuko、Nakahashi-Ouchida Rika、Mori Hiromi、Uchida Yohei、Sato Shintaro、Kurashima Yosuke、Yuki Yoshikazu、Fujihashi Kohtaro、Kawaguchi Yasushi、Kiyono Hiroshi
  • Journal Title: Mucosal Immunology Volume: 12 Issue: 6 Pages: 1391-1403
  • DOI: 10.1038/s41385-019-0203-z
  • Peer Reviewed / Open Access
• [Journal Article] Fasting-Refeeding Impacts Immune Cell Dynamics and Mucosal Immune Responses (2019)
  • Author(s): Nagai M、Noguchi R、Takahashi D、Morikawa T、Koshida K、Komiyama S、Ishihara N、Yamada T、Kawamura YI.、Muroi K、Hattori K、Kobayashi N、Fujimura Y、Hirota M、Matsumoto R、Aoki R、Tamura-Nakano M、Sugiyama M、Katakai T、Sato S、Takubo K、Dohi T、Hase K
  • Journal Title: Cell Volume: 178 Issue: 5 Pages: 1072-1087
  • DOI: 10.1016/j.cell.2019.07.047
  • Peer Reviewed
• [Journal Article] Sox8 is essential for M cell maturation to accelerate IgA response at the early stage after weaning in mice (2019)
  • Author(s): Kimura Shunsuke、Kobayashi Nobuhide、Nakamura Yutaka、Kanaya Takashi、Takahashi Daisuke、Fujiki Ryoji、Mutoh Mami、Obata Yuuki、Iwanaga Toshihiko、Nakagawa Tomoo、Kato Naoya、Sato Shintaro、Kaisho Tsuneyasu、Ohno Hiroshi、Hase Koji
  • Journal Title: The Journal of Experimental Medicine Volume: 216 Issue: 4 Pages: 831-846
  • DOI: 10.1084/jem.20181604
  • Peer Reviewed / Open Access
• [Presentation] Human norovirus propagation in human induced pluripotent stem cell-derived intestinal epithelial cells (2020)
  • Author(s): Shintaro Sato
  • Organizer: Keystone Symposia - Tissue Organoids as Models of Host Physiology and Pathophysiology of Disease (J1)
  • Int'l Joint Research
• [Presentation] Human norovirus propagation in human induced pluripotent stem cell-derived intestinal epithelial cells (2019)
  • Author(s): Shintaro Sato
  • Organizer: 19th International Congress of Mucosal Immunology
  • Int'l Joint Research
• [Book] Mucosal Vaccines, 2nd ed. - Innovation for Preventing Infections Diseases (2020)
  • Author(s): H.Kiyono & D.W.Pascual (eds.)
  • Total Pages: 915
  • Publisher: ACADEMIC PRESS, INC.
  • ISBN: 9780128119242