The role of CCR5 oligomerization in the entry of CCR5-using HIV-1

• Project/Area Number: 23590548
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Virology
• Research Institution: Kumamoto University
• Principal Investigator: MAEDA Yosuke 熊本大学, 大学院生命科学研究部, 准教授 (30284764)
• Co-Investigator(Kenkyū-buntansha): YOSHIMURA Kazuhisa 国立感染症研究所, エイズ研究センター, 室長 (60315306) ; HARADA Shinji 熊本大学, 大学院生命科学研究部, 教授 (60173085)
• Project Period (FY): 2011-04-28 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: HIV-1 / CCR5 / オリゴマー / モノマー / HIV / オリゴマー形成 / 補助受容体 / 2量体化 / リガンド

Outline of Final Research Achievements

We found that CCR5 exists as constitutive homo-oligomers, which was further enhanced by its antagonists such as maraviroc (MVC). We further showed that that CCR5 oligomer was structurally different from the monomer. Infection of oligomer- and monomer-enriched cells revealed that CCR5-using HIV-1 preferential recognized monomeric CCR5. Although CCR5 antagonists enhanced oligomerization of CCR5, MVC-resistant HIV-1 was found to still recognize both MVC-bound and -unbound forms of monomeric CCR5, suggesting the constrained use of monomeric CCR5 by R5 HIV-1.

Research Products

• [Journal Article] Separate cellular localizations of human T-lymphotropic virus 1 (HTLV-1) Env and glucose transporter type 1 (GLUT1) are required for HTLV-1 Env-mediated fusion and infection. (2015)
  • Author(s): Maeda Y, Terasawa H, Tanaka Y, Mitsuura C, Nakashima K, Yusa K, Harada S
  • Journal Title: Journal of Virlogy Volume: 89 Pages: 502-511
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Preferential recognition of monomeric CCR5 expressed in cultured cells by the HIV-1 envelope glycoprotein gp120 for the entry of R5 HIV-1 (2014)
  • Author(s): Nakano Y, Monde K, Terasawa H, Yuan Y, Yusa K, Harada S, Maeda Y
  • Journal Title: Nakano Y, Monde K, Terasawa H, Yuan Y, Yusa K, Harada S, Maeda Y Volume: 452-453 Pages: 117-124
  • DOI: 10.1016/j.virol.2013.12.034
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] V3-Independent Competitive Resistance of a Dual-X4 HIV-1 to the CXCR4 Inhibitor AMD3100 (2014)
  • Author(s): Maeda Y, Terasawa H, Nakano Y, Monde K, Yusa K, Oka S, Takiguchi M, Harada S.
  • Journal Title: PLos One Volume: 9 Issue: 2 Pages: 1-12
  • DOI: 10.1371/journal.pone.0089515
  • Peer Reviewed / Open Access
• [Journal Article] Structure and dynamics of the gp120 V3 loop that confers noncompetitive resistance in R5 HIV-1(JR-FL) to maraviroc (2013)
  • Author(s): Yuan Y, Yokoyama M, Maeda Y, Terasawa H, Harada S, Sato H, Yusa K.
  • Journal Title: PLos One Volume: 8 Issue: 6 Pages: e65115-e65115
  • DOI: 10.1371/journal.pone.0065115
  • Peer Reviewed
• [Journal Article] Promoter Targeting shRNA Suppresses HIV-1 Infection In vivo Through Transcriptional Gene Silencing (2013)
  • Author(s): Suzuki K, Hattori S, Marks K, Ahlenstiel C, Maeda Y, Ishida T, Millington M, Boyd M, Symonds G, Cooper DA, Okada S, Kelleher AD.
  • Journal Title: Mol Ther Nucleic Acids Volume: 2 Pages: e137-e137
  • DOI: 10.1038/mtna.2013.64
  • Peer Reviewed
• [Journal Article] ヒト感染が疑われたレトロウイルスの起源とウイルス安全性 (2013)
  • Author(s): 遊佐敬介・前田洋助
  • Journal Title: PHARM TEC JAPAN Volume: 28 Pages: 2075-2079
• [Journal Article] Dynamic appearance of antigenic epitopes effective for viral neutralization during membrane fusion initiated by interactions between HIV-1 envelope proteins and CD4/CXCR4. (2012)
  • Author(s): Toda T, Kuwahara K, Kondo N, Matsuda Z, Maeda Y, Maeda K, Sakaguchi N.
  • Journal Title: Immunobiology Volume: 217 Pages: 864-872
  • Peer Reviewed
• [Journal Article] Dynamic appearance of antigenic epitopes effective for viral neutralization during membrane fusion initiated by interactions between HIV-1 envelope proteins and CD4/CXCR4 (2012)
  • Author(s): Toda T, et al
  • Journal Title: Immunobiology Volume: (印刷中) Issue: 9 Pages: 864-872
  • DOI: 10.1016/j.imbio.2011.12.007
  • Peer Reviewed
• [Journal Article] A combination of polymorphic mutations in V3 loop of HIV-1 gp120 can confer noncompetitive resistance to maraviroc (2011)
  • Author(s): Yuan Y, Maeda Y, Terasawa H, Monde K, Harada S, Yusa K
  • Journal Title: Virology Volume: 413 Issue: 2 Pages: 293-299
  • DOI: 10.1016/j.virol.2011.02.019
  • 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
• [Presentation] HTLV-1 Env発現ウイルス産生細胞におけるHTLV-1受容体GLUT1の制御機構 (2014)
  • Author(s): 前田洋助，寺沢広美，光浦智将，中島詩織，門出和精，田中勇悦。遊佐敬介，原田信志
  • Organizer: 第62回日本ウイルス学会学術集会・総会
  • Place of Presentation: 横浜パシフィコ，横浜市，神奈川県
  • Year and Date: 2014-11-10 – 2014-11-12
• [Presentation] Preferential recognition of monomeric forms of CCR5 by HIV-1 envelope glycoprotein gp120 for the entry of R5 HIV-1 (2014)
  • Author(s): Nakano Y, Maeda Y, Monde K, Terasawa H, Yusa K, Harada S
  • Organizer: 14th Kumamoto AIDS seminar
  • Place of Presentation: 熊本市，熊本県
  • Year and Date: 2014-10-02 – 2014-10-03
• [Presentation] Competitive resistance of a CXCR4-using HIV-1 lacking amino acid substitutions in the V3 loop of gp120 to a CXCR4 inhibitor (2014)
  • Author(s): Terasawa H, Maeda Y, Nakano Y, Monde K, Kawano R, Yusa K, Harada S
  • Organizer: 14th Kumamoto AIDS seminar
  • Place of Presentation: 熊本市，熊本県
  • Year and Date: 2014-10-02 – 2014-10-03
• [Presentation] Competitive resistance of a CXCR4-using HIV-1 lacking amino acid substitutions in the V3 loop of gp120 to a CXCR4 inhibitor AMD3100 (2013)
  • Author(s): Terasawa H, Maeda Y, Nakano Y, Monde K, Kawano R, Yusa K, Harada S
  • Organizer: The 14th Kumamoto AIDS seminar
  • Place of Presentation: Aso Resort Grandvirio Hotel, Kumamoto, Japan
• [Presentation] Nakano Y, Maeda Y, Monde K, Terasawa H, Yusa K, Harada S: Preferential recognition of monomeric forms of CCR5 by HIV-1 envelope glycoprotein gp120 for the entry of R5 HIV-1 (2013)
  • Author(s): Nakano Y, Maeda Y, Monde K, Terasawa H, Yusa K, Harada S
  • Organizer: The 14th Kumamoto AIDS seminar
  • Place of Presentation: Aso Resort Grandvirio Hotel, Kumamoto, Japan
• [Presentation] HIV-1のcoreceptorのoligomer形成がHIV-1の感染感受性に与える影響 (2013)
  • Author(s): 中野雄介，前田洋助，門出和精，寺沢広美，遊佐敬介，原田信志
  • Organizer: 第61回日本ウイルス学会学術集会・総会
  • Place of Presentation: 神戸，神戸国際会議場
• [Presentation] CRF01_AE X4 HIV-1のCXCR4阻害剤耐性獲得機構の解析 (2013)
  • Author(s): 寺沢広美，前田洋助，中野雄介，遊佐敬介，原田信志
  • Organizer: 第27回日本エイズ学会学術集会・総会
  • Place of Presentation: 熊本，熊本市民会館
• [Presentation] HIV-1 coreceptorのoligomer形成がHIV-1感染感受性に与える影響 (2012)
  • Author(s): 中野雄介，前田洋助，門出和精，寺沢広美，遊佐敬介，原田信志
  • Organizer: 第60回日本ウイルス学会学術集会・総会
  • Place of Presentation: グランキューブ大阪
• [Presentation] CRF01_AE X4 HIVのV3非依存的CXCR4阻害剤逃避 (2012)
  • Author(s): 寺沢広美，前田洋助，河野里奈，中野雄介，門出和精，遊佐敬介，原田信志
  • Organizer: 第26回日本エイズ学会学術集会・総会
  • Place of Presentation: 慶應義塾大学日吉キャンパス
• [Presentation] Reversion of CXCR4-using CRF01_A/E to CCR5-using HIV-1 by a CXCR4 antagonists in vitro (2011)
  • Author(s): Maeda Y, Terasawa H, Ishiguro H, Nakano Y, Harada S
  • Organizer: XV International Congress of Virology
  • Place of Presentation: Sapporo Convention Center, Sapporo, Japan