Establishment of in vitro selection system using recent primary isolates, and a new efficient treatment for HIV

• Project/Area Number: 22790163
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Medical pharmacy
• Research Institution: Kumamoto University
• Principal Investigator: HARADA Shigeyoshi 熊本大学, エイズ学研究センター, COEリサーチ・アソシエイト (30508643)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: オーダーメード医療 / HIV / HIV-1 / 薬剤耐性 / 臨床分離株 / ウイルス / 感染症 / 免疫学

Research Abstract

In vitro selection with anti-HIV-1 drugs were used to obtain genetically heterogeneous primary HIV-1 isolates. Env diversities significantly decreased during in vitro selection. Furthermore, these drugs-selected variants had completely different Env sequences from that in the passage control. This study is the first to explore the influence of anti-HIV drugs on genetic bottlenecks in bulk HIV primary isolates containing highly diverse Env sequences using in vitro selection methods. In vitro selection may be a useful tool for investigating the compatibility of combined anti-retroviral therapy using entry inhibitors.

Research Products

• [Journal Article] In vitro and In vivo Resistance to Human Immunodeficiency Virus Type 1 Entry Inhibitors (2011)
  • Author(s): Maeda, Y., Yoshimura, K., Miyamoto, F., Kodama, E., Harada, S., Yuan, Y., Harada, S., and Yusa, K
  • Journal Title: J AIDS Clinic Res
  • Peer Reviewed
• [Journal Article] Small molecular CD4 mimics as HIV entry inhibitors (2011)
  • Author(s): Narumi, T., Arai, H., Yoshimura, K., Harada, S., Nomura, W., Matsushita, S., Tamamura. H
  • Journal Title: Bioorg Med Chem Volume: 19 Pages: 6735-6742
  • Peer Reviewed
• [Journal Article] Small Molecular CD4 Mimics as HIV Entry Inhibitors (2011)
  • Author(s): Narumi T, Nomura W, Matsushita S, Tamamura H, et al.
  • Journal Title: Bioorg Med Chem Volume: 19 Issue: 22 Pages: 6735-6742
  • DOI: 10.1016/j.bmc.2011.09.045
  • Peer Reviewed
• [Journal Article] In vitro and In vivo Resistance to Human Immunodeficiency Virus Type 1 Entry Inhibitors (2011)
  • Author(s): Maeda, Y.
  • Journal Title: J AIDS Clinic Res Volume: in press Issue: S2
  • DOI: 10.4172/2155-6113.s2-004
  • Peer Reviewed
• [Journal Article] CD4 mimics targeting the HIV entry mechanism and their hybrid molecules with a CXCR4 antagonist (2010)
  • Author(s): Narumi, T., Ochiai, C., Yoshimura, K., Harada, S., Tanaka, T., Nomura, W., Arai, H., Ozaki, T., Ohashi, N., Matsushita, S., Tamamura, H
  • Journal Title: Bioorg Med Chem Lett Pages: 5853-5858
  • Peer Reviewed
• [Journal Article] Enhanced exposure of human immunodeficiency virus type 1 primary isolate neutralization epitopes through binding of CD4 mimetic compounds (2010)
  • Author(s): Yoshimura, K., Harada, S., Shibata, J., Hatada, M., Yamada, Y., Ochiai, C., Tamamura, H., Matsushita S
  • Journal Title: J. Virol Volume: 84 Pages: 7558-7568
  • Peer Reviewed
• [Journal Article] HIV-1 evasion of a neutralizing anti-V3 antibody involves acquisition of a potential glycosylation site in V2 (2010)
  • Author(s): Hatada, M., Yoshimura, K., Harada, S., Kawanami, Y., Shibata, J., Matsushita S
  • Journal Title: J. Gen. Virol Volume: 91 Pages: 1335-1345
  • Peer Reviewed
• [Journal Article] CD4 mimics targeting the mechanism of HIV entry (2010)
  • Author(s): Yamada, Y., Ochiai, C., Yoshimura, K., Tanaka, T., Ohashi, N., Narumi, T., Nomura, W., Harada, S., Matsushita, S., Tamamura. H
  • Journal Title: Bioorg Med Chem Lett Volume: 20 Pages: 354-358
  • Peer Reviewed
• [Journal Article] CD4 mimics targeting the HIV entry mechanism and their hybrid molecules with a CXCR4 antagonist. (2010)
  • Author(s): Narumi T
  • Journal Title: Bioorg Med Chem Lett. Volume: 20 Pages: 5853-8
  • Peer Reviewed
• [Journal Article] Enhanced exposure of human immunodeficiency virus type 1 primary isolate neutralization epitopes through binding of CD4 mimetic compounds. (2010)
  • Author(s): Yoshimura K
  • Journal Title: J Virol. Volume: 84 Pages: 7558-68
  • Peer Reviewed
• [Journal Article] Human immunodeficiency virus type 1 evasion of a neutralizing anti-V3 antibody involves acquisition of a potential glycosylation site in V2 (2010)
  • Author(s): Hatada M
  • Journal Title: J Gen Virol. Volume: 91 Pages: 1335-45
  • Peer Reviewed
• [Presentation] 抗HIV剤がEnv多様性に与える影響 (2011)
  • Author(s): 原田恵嘉、濱治有希、遊佐敬介、松下修三、吉村和久
  • Organizer: 第25回日本エイズ学会学術集会・総会
  • Place of Presentation: ハイアットリージェンシー東京(東京)
  • Year and Date: 2011-12-01
• [Presentation] 抗HIV剤がEnv多様性に与える影響 (2011)
  • Author(s): 原田恵嘉
  • Organizer: 第25回日本エイズ学会学術集会・総会
  • Place of Presentation: ハイアット リージェンシー東京(東京都)
  • Year and Date: 2011-12-01
• [Presentation] Impact of raltegravir pressure on the selection of HIV-1 envelope sequences in vitro (2011)
  • Author(s): Harada S., Ishikawa T., Hamji A., Matsushita S., Yoshimura K
  • Organizer: 12th Kumamoto AIDS Seminar GCOE Joint International Symposium
  • Place of Presentation: Aso Resort GRANDVRIO Hotel(Kumamoto, Japan)
  • Year and Date: 2011-10-21
• [Presentation] Impact of raltegravir pressure on the selection of HIV-1 envelope sequences in vitro (2011)
  • Author(s): Harada, S.
  • Organizer: 12th Kumamoto AIDS Seminar GCOE Joint International Symposium
  • Place of Presentation: Aso Resort GRANDVRIO Hotel (Kumaraoto, Japan)
  • Year and Date: 2011-10-21
• [Presentation] Evolution and selection of the env gene of HIV-1 primary isolates during in vitro selection of raltegravir (2011)
  • Author(s): Harada S., Hamji A., Matsushita S., Yoshimura K
  • Organizer: 11th Kumamoto AIDS Seminar GCOE Joint International Symposium
  • Place of Presentation: Aso Resort GRANDVRIO Hotel(Kumamoto, Japan)
  • Year and Date: 2011-10-08
• [Presentation] Impact of raltegravir pressure on the selection of HIV-1 envelope sequences in vitro (2011)
  • Author(s): Harada S., Ishikawa T., Hamji A., Matsushita S., Yoshimura K
  • Organizer: 6th IAS Conference on HIV Pathogenesis, Treatment and Prevention
  • Place of Presentation: Auditorium Parco della Musica(Roma, Italy)
  • Year and Date: 2011-07-17
• [Presentation] Impact of raltegravir pressure on the selection of HIV-1 envelope sequences in vitro (2011)
  • Author(s): Harada, S.
  • Organizer: 6th IAS Conference on HIV Pathogenesis, Treatment and Prevention
  • Place of Presentation: Auditorium Parco della Musica (Roma, Italy)
  • Year and Date: 2011-07-17
• [Presentation] ラルテグラビルはHIV-1のin vitro馴化におけるEnv選択に影響する (2010)
  • Author(s): 原田恵嘉、濱治有希、松下修三、吉村和久
  • Organizer: 第24回日本エイズ学会学術集会・総会
  • Place of Presentation: ザ・プリンスさくらタワー東京(東京)
  • Year and Date: 2010-11-25
• [Presentation] ラルテグラビルはHIV-1のin vitro馴化におけるEnv選択に影響する (2010)
  • Author(s): 原田恵嘉
  • Organizer: 第24回日本エイズ学会学術集会・総会
  • Place of Presentation: (東京)グランドプリンスホテル高輪
  • Year and Date: 2010-11-25
• [Remarks]
  • URL: http://yoshimura-project.p1.bindsite.jp/index.html
• [Remarks]
  • URL: http://yoshimura-project.pl.bindsite.jp/index.html