In vivo analysis of HIV transmission via dendritic cells in humanized mice

• Project/Area Number: 26460500
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: Terahara Kazutaka 国立感染症研究所, 免疫部, 主任研究官 (50469954)
• Co-Investigator(Renkei-kenkyūsha): YOKOTA Yasuko 東京工科大学, 医療保健学部, 教授 (20182701)
• Research Collaborator: IWABUCHI Ryutaro
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: ヒト化マウス / 樹状細胞 / HIV / T細胞 / サイトカイン / 骨髄系細胞

Outline of Final Research Achievements

This study was aimed at elucidating the role of dendritic cells (DCs) on HIV-1 transmission in vivo using humanized mice. Because the development of myeloid-lineage immune cells including DCs is poor in conventional humanized mice, introduction of human GM-CSF and Flt3-L into humanized mice was tested to induce DCs. As a result, two myeloid DC subsets, BDCA-1+ MDC1 and BDCA-3+ MDC2, were significantly induced by treatment with these cytokines. When these DC-induced humanized mice and control humanized mice were infected with HIV-1, a significant correlation between the absolute cell number of blood monocytes pre-infection and the plasma viral load at 1 week post-infection was observed. This result suggests that DCs are involved in the efficacy of HIV-1 transmission in vivo at the early phase of infection.

Research Products

• [Journal Article] A humanized mouse model identifies key amino acids for low immunogenicity of H7N9 vaccines. (2017)
  • Author(s): Wada Y, Nithichanon A, Nobusawa E, Moise L, Martin W, Yamamoto N, Terahara K, Hagiwara H, Odagiri T, Tashiro M, Lertmemongkolchai G, Takeyama H, Groot AD, Ato M, Takahashi Y.
  • Journal Title: Sci. Rep. Volume: 7 Issue: 1 Pages: 1283-1283
  • DOI: 10.1038/s41598-017-01372-5
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Homeostatically Maintained Resting Naive CD4+ T Cells Resist Latent HIV Reactivation. (2016)
  • Author(s): Tsunetsugu-Yokota Y, Kobayahi-Ishihara M, Wada Y, Terahara K, Takeyama H, Kawana-Tachikawa A, Tokunaga K, Yamagishi M, Martinez JP, Meyerhans A.
  • Journal Title: Front. Microbiol. Volume: 7 Pages: 1944-1944
  • DOI: 10.3389/fmicb.2016.01944
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A novel dual luciferase assay for the simultaneous monitoring of HIV infection and cell viability (2016)
  • Author(s): Mitsuki Y-y, Yamamoto T, Mizukoshi F, Momota M, Terahara K, Yoshimura K, Harada S, Tsunetsugu-Yokota Y
  • Journal Title: Journal of Virological Methods Volume: 231 Pages: 25-33
  • DOI: 10.1016/j.jviromet.2016.02.006
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Humanized mice dually challenged with R5 and X4 HIV-1 show preferential R5 viremia and restricted X4 infection of CCR5+CD4+ T cells. (2015)
  • Author(s): Terahara, K., Ishige, M., Ikeno, S., Okada, S., Kobayashi-Ishihara, M., Ato, M., and Tsunetsugu-Yokota, Y
  • Journal Title: Microbes and Infection Volume: 10.1016/j.micinf.2015.02.002 Issue: 5 Pages: 378-386
  • DOI: 10.1016/j.micinf.2015.02.002
  • Peer Reviewed
• [Presentation] Exploring a mechanism of HIV latency in homeostatically maintained CD4+ T cells. (2016)
  • Author(s): Kobayashi-Ishihara M, Martinez J.P., Terahara K., Meyerhans A., Tsunetsugu-Yokota Y.
  • Organizer: 第46回日本免疫学会総会・学術集会
  • Place of Presentation: 沖縄
  • Year and Date: 2016-12-05
• [Presentation] Analysis of proviral genome sequences in lymph nodes in SIV-infected rhesus macaques. (2016)
  • Author(s): Nomura T, Yamamoto H, Terahara K, Seki S, Matano T.
  • Organizer: 2nd Kumamoto IRCMS International Symposium and 17th Kumamoto AIDS Seminar
  • Place of Presentation: 熊本
  • Year and Date: 2016-10-31
  • Int'l Joint Research
• [Presentation] Proviral genome sequences in lymph nodes and bone marrows in SIV-infected rhesus macaques. (2016)
  • Author(s): Nomura T, Yamamoto H, Terahara K, Seki S, Matano T.
  • Organizer: 第64回日本ウイルス学会学術集会
  • Place of Presentation: 札幌
  • Year and Date: 2016-10-23
• [Presentation] Maintenance of HIV latency by HIV-1 encoded antisense RNAs. (2016)
  • Author(s): Kobayashi-Ishihara M, Terahara K, Ato M, Tsunetsugu-Yokota Y.
  • Organizer: 第64回日本ウイルス学会学術集会
  • Place of Presentation: 札幌
  • Year and Date: 2016-10-23
• [Presentation] Analysis of proviral genome sequences in multiple cell subsets in SIV-infected rhesus macaques. (2016)
  • Author(s): Nomura T, Yamamoto H, Terahara K, Seki S, Matano T.
  • Organizer: The 34th annual symposium on non-human primate models for AIDS
  • Place of Presentation: New Orleans, LA, USA
  • Year and Date: 2016-10-11
  • Int'l Joint Research
• [Presentation] HIV-1感染初期におけるCD4陽性T細胞の細胞死誘導とcaspase分子群の関連について：ヒト化マウスモデルでの解析 (2016)
  • Author(s): 寺原和孝、岩渕龍太郎、小林―石原美栄、横田―恒次恭子
  • Organizer: 第89回日本生化学会大会
  • Place of Presentation: 仙台
  • Year and Date: 2016-09-25
• [Presentation] アンチセンス鎖を介したHIV-1潜伏化制御について (2015)
  • Author(s): 小林―石原美栄、寺原和孝、池野翔太、阿戸学、横田―恒次恭子
  • Organizer: 第38回日本分子生物学会年会 第88回日本生化学会大会 合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2015-12-01
• [Presentation] Induction of human cytokines in humanized mice improves myeloid cell development and antigen-specific antibody production (2014)
  • Author(s): Ikeno S., Terahara K., Tsunetsugu-Yokota Y
  • Organizer: 第43回日本免疫学会総会・学術集会
  • Place of Presentation: 京都
  • Year and Date: 2014-12-12
• [Presentation] 恒常的に培養維持されたCD4陽性T細胞へのHIV-1の感染とその転写制御機構の解明 (2014)
  • Author(s): 和田倭、小林（石原）美栄、寺原和孝、池野翔太、徳永研三、立川（川名）愛、山岸誠、竹山春子、横田（恒次）恭子
  • Organizer: 第62回日本ウイルス学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2014-11-12
• [Presentation] ヒト化マウスの麻疹ウイルスベクター評価系への応用（3） (2014)
  • Author(s): 池野翔太、寺原和孝、駒瀬勝啓、竹田誠、森川裕子、竹山春子、横田（恒次）恭子
  • Organizer: 第62回日本ウイルス学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2014-11-11
• [Presentation] R5・X4 HIV-1混在感染ヒト化マウスの感染早期にみられるR5ウイルス優位性とその要因の検討 (2014)
  • Author(s): 寺原和孝、石毛真行、池野翔太、小林（石原）美栄、岡田誠治、横田（恒次）恭子
  • Organizer: 第62回日本ウイルス学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2014-11-10