Visualization of immune cell-to-cell transmission of SFTS virus

• Project/Area Number: 21K20768
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0803:Pathology, infection/immunology, and related fields
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: Sho Miyamoto 国立感染症研究所, 感染病理部, 研究員 (30881792)
• Project Period (FY): 2021-08-30 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000); Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: SFTS virus / B cell / preplasmablast / B細胞活性化 / 形質芽球 / IL-6 / Electron microscopy / Plasmablast / Monocyte

Outline of Research at the Start

重症熱性血小板減少症候群 (Severe fever with thrombocytopenia syndrome, SFTS) は SFTS ウイルスがもたらすウイルス性出血熱の一つである。出血熱ウイルスの多くは単球系細胞を感染標的とするが、SFTS ウイルスはB細胞を感染標的とすることが分かってきた。しかし、B細胞はSFTSウイルスの既知の侵入レセプターを持たないため、なぜ SFTSウイルスが B細胞に感染できるのかが不明である。本研究では、 培養細胞や臨床検体の遺伝子発現解析と感染細胞動態の可視化からB細胞のウイルス感受性が増強される条件を決定し、 B細胞への感染機構を明らかにする。

Outline of Final Research Achievements

The B cells that are the target of SFTS virus infection in humans are activated B cells that differentiated into plasmablasts. To elucidate how the target cells are induced, we performed SFTS virus infection of human peripheral blood cells, verified whether activated B cells are induced, and searched for cell types and secreted factors required for the induction. After infecting peripheral blood cells with SFTS virus, we observed the induction of the activated B cells with a phenotype similar to that of atypical lymphocytes in SFTS patients. Notably, infection of peripheral blood B cells alone induced similar activated B cell propagation. Cytokine quantification revealed secreted factors specific to B cells that were not secreted by the virus-infected monocytes.

Academic Significance and Societal Importance of the Research Achievements

末梢血B細胞へのウイルス感染のみで活性化B細胞が増殖することから、その誘導にはSFTSウイルスのB細胞感染が重要であると考えられた。また、B細胞感染によって分泌されるサイトカイン・ケモカインが活性化B細胞の増殖を促すことが示唆された。これらの成果はSFTS患者の生体内におけるウイルス増殖と標的免疫細胞の動態の解明に寄与し、SFTS重症化機構の解明に貢献すると考えられる。

Research Products

• [Journal Article] Migration of Influenza Virus Nucleoprotein into the Nucleolus Is Essential for Ribonucleoprotein Complex Formation (2022)
  • Author(s): Sho Miyamoto, Masahiro Nakano, Takeshi Morikawa, Ai Hirabayashi, Ryoma Tamura, Yoko Fujita-Fujiharu, Nanami Hirose, Yukiko Muramoto, and Takeshi Noda
  • Journal Title: mBio Volume: 13 Issue: 1
  • DOI: 10.1128/mbio.03315-21
  • Peer Reviewed / Open Access
• [Journal Article] Duration of Infectious Virus Shedding by SARS-CoV-2 Omicron Variant?Infected Vaccinees (2022)
  • Author(s): Takahashi K, Ishikane M, Ujiie M, Iwamoto N, Okumura N, Sato T, Nagashima M, Moriya A, Suzuki M, Hojo M, Kanno T, Saito S, Miyamoto S, Ainai A, Tobiume M, Arashiro T, Fujimoto T, Saito T, Yamato M, Suzuki T, Ohmagari N.
  • Journal Title: Emerging Infectious Diseases Volume: 28 Issue: 5 Pages: 998-1001
  • DOI: 10.3201/eid2805.220197
  • Peer Reviewed / Open Access
• [Journal Article] Contribution of RNA-RNA Interactions Mediated by the Genome Packaging Signals for the Selective Genome Packaging of Influenza A Virus. (2022)
  • Author(s): Miyamoto S, Muramoto Y, Shindo K, Fujita-Fujiharu Y, Morikawa T, Tamura R, Gilmore JL, Nakano M, Noda T.
  • Journal Title: J Virol Volume: 96 Issue: 6
  • DOI: 10.1128/jvi.01641-21
  • Peer Reviewed / Open Access
• [Journal Article] Vaccination-infection interval determines cross-neutralization potency to SARS-CoV-2 Omicron after breakthrough infection by other variants (2022)
  • Author(s): Miyamoto S, Arashiro T, Adachi Y, Moriyama S, Kinoshita H, Fukushi S, Takahashi Y, Suzuki T et al.
  • Journal Title: Med Volume: 3 Issue: 4 Pages: 249-261
  • DOI: 10.1016/j.medj.2022.02.006
  • Peer Reviewed / Open Access
• [Journal Article] A Fatal Breakthrough Coronavirus Disease 2019 Case Following Bendamustine?Rituximab Therapy (2022)
  • Author(s): Kamegai Kohei、Iwamoto Noriko、Togano Tomiteru、Maeda Kenji、Takamatsu Yuki、Miyazato Yusuke、Ishikane Masahiro、Mizokami Masashi、Sugiyama Masaya、Iida Shun、Miyamoto Sho、Suzuki Tadaki、Ohmagari Norio
  • Journal Title: International Journal of Infectious Diseases Volume: - Pages: 85-88
  • DOI: 10.1016/j.ijid.2022.04.058
  • Peer Reviewed
• [Journal Article] 特集 グローバル時代の新興再興感染症への科学的アプローチ Ⅲ.デング･ジカ･SFTS･出血熱へのアプローチ SFTS患者検体を用いた病理学的探索によるウイルス性出血熱の新規発病機構の発見 (2021)
  • Author(s): 宮本 翔、鈴木 忠樹
  • Journal Title: 生体の科学 Volume: 72 Issue: 4 Pages: 311-315
  • DOI: 10.11477/mf.2425201374
  • ISSN: 0370-9531, 1883-5503
  • Year and Date: 2021-08-15
• [Journal Article] Propagation of Activated B Cells by In Vitro Severe Fever With Thrombocytopenia Syndrome Virus Infection of Human Peripheral Blood Mononuclear Cells (2021)
  • Author(s): Wada Yuji、Miyamoto Sho、Iida Shun、Sano Kaori、Sato Yuko、Ainai Akira、Saito Kumpei、Katano Harutaka、Hasegawa Hideki、Suzuki Tadaki
  • Journal Title: The Journal of Infectious Diseases Volume: 225 Issue: 2 Pages: 269-281
  • DOI: 10.1093/infdis/jiab343
  • Peer Reviewed
• [Journal Article] CP100356 Hydrochloride, a P-Glycoprotein Inhibitor, Inhibits Lassa Virus Entry: Implication of a Candidate Pan-Mammarenavirus Entry Inhibitor (2021)
  • Author(s): Takenaga T, Zhang Z, Muramoto Y, Fehling SK, Hirabayashi A, Takamatsu Y, Kajikawa J, Miyamoto S, Nakano M, Urata S, Groseth A, Strecker T, Noda T.
  • Journal Title: Viruses Volume: 13 Issue: 9 Pages: 1763-1763
  • DOI: 10.3390/v13091763
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] SFTSウイルス感染による活性化B細胞誘導機構の探索 (2021)
  • Author(s): 宮本翔 , 和田雄治 , 飯田俊 , 佐野芳 , 佐藤由子 , 相内章 , 齋藤訓平 , 片野晴隆 , 長谷川秀樹 , 鈴木忠樹
  • Organizer: 第3回 SFTS研究会・学術集会
• [Presentation] SFTSウイルスの生体内感染標的細胞の誘導機構 (2021)
  • Author(s): 宮本翔
  • Organizer: ウイルス若手研究集会2021 O-05