Study for the mechanism of HIV-1 latent infection in a humanized mouse model

• Project/Area Number: 23790453
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• 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)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: HIV / ヒト化マウス / T細胞 / HIV-1 / 樹状細胞

Research Abstract

This study was aimed at elucidating the mechanism of latent infection of HIV-1 by analyzing a humanized mouse model. Humanized mice were challenged with CXCR4-tropic (X4) and/or CCR5-tropic (R5) HIV-1. We found that R5 HIV-1 preferentially targeted to activated memory CD4+ T cells irrespective of X4 HIV-1. In contrast, although X4 HIV-1 substantially infected to activated memory CD4+ T cells, the infection efficiency in the cell population was markedly reduced in the presence of R5 HIV-1. These results suggest that the respective X4 and R5 HIV-1 reservoirs are formed from different subsets of CD4+ T cells.

Research Products

• [Journal Article] Sensitive detection of measles virus infection in the blood and tissues of humanized mouse by one-step quantitative RT-PCR (2013)
  • Author(s): Shota Ikeno, Moto-omi Suzuki, Mahmod Muhsen, Masayuki Ishige, Mie Kobayashi, Shinji Ohno, Makoto Takeda, Tetsuo Nakayama, Yuko Morikawa, Kazutaka Terahara, Seiji Okada, Haruko Takeyama, Yasuko Tsunetsugu-Yokota
  • Journal Title: Frontiers in Microbiology Volume: 4 Pages: 298-298
  • DOI: 10.3389/fmicb.2013.00298
  • Peer Reviewed
• [Journal Article] Expansion of activated memory CD4+ T cells affects infectivity of CCR5-tropic HIV-1 in humanized NOD/SCID/JAK3null mice (2013)
  • Author(s): Kazutaka Terahara, Masayuki Ishige, Shota Ikeno, Yu-ya Mitsuki, Seiji Okada, Kazuo Kobayashi, Yasuko Tsunetsugu-Yokota
  • Journal Title: PLoS ONE Volume: 8(1) Issue: 1 Pages: 8-8
  • DOI: 10.1371/journal.pone.0053495
  • Peer Reviewed
• [Journal Article] HIV-1 infection ex vivoaccelerates measles virus infection by upregulating signaling lymphocytic activation molecule (SLAM) in CD4+T cells (2012)
  • Author(s): Mitsuki Y, Terahara K, Shibusawa K, Yamamoto T, Tsuchiya T, Ishige M, Kobayashi K, Morikawa Y, Nakayama T, Takeda M, Yanagi Y, Tsunetsugu-Yokota Y
  • Journal Title: J Virol Volume: 86 Issue: 13 Pages: 7227-7234
  • DOI: 10.1128/jvi.06681-11
  • Peer Reviewed
• [Journal Article] Association of major histocompatibility complex class I haplotypes with disease progression after simian immunodeficiency virus challenge in Burmese rhesus macaques (2012)
  • Author(s): Nomura, T., Yamamoto, H., Shiino, T., Takahashi, N., Nakane, T., Iwamoto, N., Ishii, H., Tsukamoto, T., Kawada, M., Matsuoka, S., Takeda, A., Terahara, K., Tsunetsugu-Yokota, Y., Iwata-Yoshikawa, N., Hasegawa, H., Sata, T., Naruse T.K., Kimura, A., Matano, T.
  • Journal Title: Journal of Virology Volume: (in press) Issue: 12 Pages: 6481-90
  • DOI: 10.1128/jvi.07077-11
  • Peer Reviewed
• [Journal Article] Receptor usage and the pathogenesis in acute and chronic virus infections (2012)
  • Author(s): Yasuko Tsunetsugu-Yokota, Kazutaka Terahara
  • Journal Title: Frontiers in Microbiology Volume: 3 Pages: 289-289
  • DOI: 10.3389/fmicb.2012.00289
  • Peer Reviewed
• [Journal Article] Fluorescent reporter signals, EGFP and DsRed, encoded in HIV-1 facilitate the detection of productively infected cells and cell-associated viral replication levels (2012)
  • Author(s): K. Terahara, T. Yamamoto, Y. Mitsuki, K. Shibusawa, M. Ishige, F. Mizukoshi, K. Kobayashi, Y. Tsunetsugu-Yokota
  • Journal Title: Frontiers in Microbiology Volume: 2 Pages: 280-280
  • DOI: 10.3389/fmicb.2011.00280
  • Peer Reviewed
• [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(II) (2013)
  • Author(s): 池野翔太、鈴木基臣、寺原和孝、石毛真行、駒瀬勝啓、竹田誠、森川裕子、中川哲夫、柳雄介、竹山春子、横田(恒次)恭子
  • Organizer: 第61回日本ウイルス学会学術集会
  • Place of Presentation: 神戸
• [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（II） (2013)
  • Author(s): 池野翔太、鈴木基臣、寺原和孝、石毛真行、駒瀬勝啓、竹田誠、森川裕子、中川哲夫、柳雄介、竹山春子、横田（恒次）恭子
  • Organizer: 第61回日本ウイルス学会学術集会
  • Place of Presentation: 神戸
• [Presentation] Humanized mice as an animal model for human-tropic virus infection (2012)
  • Author(s): Y. Tsunetsugu-Yokota, M. Ishige, S. Ikeno, K. Terahara
  • Organizer: Immunological Mechanisms of Vaccination
  • Place of Presentation: Keystone Symposia, Ottawa, Ontario, Canada
• [Presentation] Application of humanized mice for the evaluation of measles virus vector (2012)
  • Author(s): S. Ikeno, K. Terahara, M. Ishige, M. Suzuki, Y.-y. Mitsuki, Y. Morikawa, T. Nakayama, Y. Tsunetsugu-Yokota
  • Organizer: The 11th Awaji International Forum on Infection and Immunity
  • Place of Presentation: Awaji, Hyogo, Japan
• [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 (2012)
  • Author(s): 池野翔太、寺原和孝、石毛真行、鈴木基臣、光木裕也、森川裕子、中川哲夫、横田恭子
  • Organizer: 第60回日本ウイルス学会学術集会
  • Place of Presentation: 大阪
• [Presentation] キャピラリープレートを用いた単一細胞解析のためのデジタルPCR法の開発とHIV研究へのアプローチ (2012)
  • Author(s): 鈴木基臣、モリテツシ、寺原和孝、横田(恒次)恭子、竹山春子
  • Organizer: 第6回バイオ関連化学シンポジウム
  • Place of Presentation: 札幌
• [Presentation] サルエイズモデルにおけるヘルパーT細胞反応の解析 (2012)
  • Author(s): 寺原和孝
  • Organizer: 第14回白馬シンポジウムin京都
  • Place of Presentation: 京都
• [Presentation] Humanized mice as an animal model for human-tropic virus infection. Immunological Mechanisms of Vaccination (2012)
  • Author(s): Y. Tsunetsugu-Yokota, M. Ishige, S. Ikeno, K. Terahara
  • Organizer: Keystone Symposia
  • Place of Presentation: Ottawa, Ontario, Canada
• [Presentation] R5およびX4 HIV-1同時感染ヒト化マウスモデルによる感染早期のウイルス優位性の解析 (2011)
  • Author(s): 石毛真行、寺原和孝、渋沢謙太郎、光木裕也、池野翔太、小林和夫、岡田誠治、横田(恒次)恭子
  • Organizer: 第25回日本エイズ学会学術集会
  • Place of Presentation: 東京
• [Presentation] 麻疹ウイルス偽型化HIV-1抑制性shRNA発現レンチウイルスベクターのヒト化マウスにおけるin vivo評価 (2011)
  • Author(s): 渋沢謙太郎、寺原和孝、石毛真行、光木裕也、横田(恒次)恭子
  • Organizer: 第25回日本エイズ学会学術集会
  • Place of Presentation: 東京