Study of novel HIV restriction factors

• Project/Area Number: 23659229
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Virology
• Research Institution: Kyoto University
• Principal Investigator: KOYANAGI Yoshio 京都大学, ウイルス研究所, 教授 (80215417)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2012: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000); Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: AIDS / HIV / restriction factor / SAMHD1 / Vpx / マクロファージ / HSV / nucleotidase / 単球

Research Abstract

Accumulating evidences have suggested that the host cells possess intrinsic anti-viral factors. SAMHD1 is a newly identified anti-HIV host factor that has a dNTP triphosphohydrolase activity and depletes intracellular dNTP pools in non-dividing myeloid cells. Since DNA viruses utilize cellular dNTPs, we investigated whether SAMHD1 limits the replication of DNA viruses in non-dividing myeloid target cells. Indeed, a double stranded DNA viruses, herpes simplex virus type 1, are subject to SAMHD1 restriction in non-dividing target cells in a dNTP dependent manner. This study suggests that SAMHD1 is a potential innate anti-viral player that suppresses the replication of a wide range of DNA viruses as well as retroviruses that infect non-dividing myeloid cells during infection.

Research Products

• [Journal Article] Quantification of the dynamics of enterovirus 71 infection by experimental-mathematical investigation (2013)
  • Author(s): Fukuhara M, Iwami S, Sato K, Nishimura Y, Shimizu H, Aihara K, Koyanagi Y
  • Journal Title: J Virol Volume: 87 Issue: 1 Pages: 701-705
  • DOI: 10.1128/jvi.01453-12
  • Peer Reviewed
• [Journal Article] Vpu and BST2: still not there yet? (2012)
  • Author(s): Sato K., Gee P., Koyanagi Y.
  • Journal Title: Frontiers in Microbiology Volume: 3 Pages: 131-131
  • DOI: 10.3389/fmicb.2012.00131
  • Peer Reviewed
• [Journal Article] Identifying viral parameters from in vitro cell cultures. (2012)
  • Author(s): Iwami, S.
  • Journal Title: Front. Microbiol. Volume: 3 Pages: 319-319
  • DOI: 10.3389/fmicb.2012.00319
  • Peer Reviewed
• [Journal Article] Vpu augments the initial burst phase of HIV-1 propagation and downre gulates BST2 and CD4 in humanized mice (2012)
  • Author(s): Sato, K.
  • Journal Title: J Virol. Volume: 86 Issue: 9 Pages: 5000-5013
  • DOI: 10.1128/jvi.07062-11
  • Peer Reviewed
• [Journal Article] Integrase-independent HIV-1 infection is augmented under conditions of DNA damage and produces a viral reservoir (2012)
  • Author(s): Ebina H, Kanemura Y, Suzuki Y, Urata K, Misawa N, Koyanagi Y
  • Journal Title: Virology Volume: 427 Issue: 1 Pages: 44-50
  • DOI: 10.1016/j.virol.2012.02.004
  • NAID: 120004007474
  • Peer Reviewed
• [Journal Article] Rho GTPase inhibitorARHGDIB/D4GDI limits HIV-1 replication (2011)
  • Author(s): Watanabe T, Urano E, Koyanagi Y, KomanoJ, 10人中9番目
  • Journal Title: AIDS Research and Human Retroviruses Volume: (印刷中) Issue: 8 Pages: 1-10
  • DOI: 10.1089/aid.2011.0180
  • Peer Reviewed
• [Journal Article] APOBEC1-mediated editing and attenuation of herpes simplex virus 1 DNA indicate that neurons have an antiviral role during herpes simplex encephalitis (2011)
  • Author(s): Gee P, Ando Y, Kitayama H, Yamamoto SP, Kanemura Y, Ebina H, Kawaguchi Y, Koyanagi Y
  • Journal Title: Journal of Virology Volume: 85 Issue: 19 Pages: 9726-9736
  • DOI: 10.1128/jvi.05288-11
  • Peer Reviewed
• [Journal Article] A novel animal model of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis in humanized mice (2011)
  • Author(s): Sato K, Misawa N, Nie C, Satou Y, Iwakiri D, Matsuoka M, Takahashi R, Kuzushima K, Ito M, Takada K, Koyanagi Y
  • Journal Title: Blood Volume: 117 Issue: 21 Pages: 5663-5673
  • DOI: 10.1182/blood-2010-09-305979
  • Peer Reviewed
• [Journal Article] The mouse is out of the bag : insights and perspectives on HIV-1-infected humanized mouse models (review) (2011)
  • Author(s): Sato K, Koyanagi Y
  • Journal Title: Experimental Biology and Medicine Volume: 236 Issue: 8 Pages: 977-985
  • DOI: 10.1258/ebm.2011.010294
  • Peer Reviewed
• [Journal Article] Huwe1, a novel cellular interactor of Gag-Pol through integrase binding, negatively influences HIV-1 infectivity (2011)
  • Author(s): Yamamoto SP, Okawa K, Nakano T, Sano K, Ogawa K, Masuda T, Morikawa Y, Koyanagi Y, Suzuki Y
  • Journal Title: Mcirobes Infect Volume: 13 Issue: 4 Pages: 339-349
  • DOI: 10.1016/j.micinf.2010.12.002
  • Peer Reviewed
• [Journal Article] APOBEC1-mediated editing and attenuation of herpes simplex virus 1 DNA indicate that neurons have an antiviral role during herpes simplex encephalitis (2011)
  • Author(s): Gee P, Ando Y, Kitayama H, Yamamoto SP, Kanemura Y, Ebina H, Kawaguchi Y, Koyanagi Y
  • Journal Title: Journal of Virology Volume: 85 Pages: 9726-9736
  • NAID: 120003497115
  • Peer Reviewed
• [Journal Article] Host factor SAMHD1 restricts DNA viruses in non-dividing myeloid cells
  • Author(s): Hollenbaugh JA, Gee P, Baker J, Daly MB, Amie S, Kasai N, Kanemura Y, Ward BM, Koyanagi Y, Kim B
  • Journal Title: PLoS Pathog Volume: (印刷中)
  • Peer Reviewed
• [Presentation] レトロウイルス感染におけるエフェクター分子北海道大学遺伝子制御研究所研究集会 (2012)
  • Author(s): 小柳義夫
  • Organizer: 感染と癌 -感染癌のエフェクター分子とその標的
  • Place of Presentation: 北海道大学医学部学友会館(札幌)
  • Year and Date: 2012-09-18
• [Presentation] Positive contribution of HIV-1 Vpu for viral propagation in vivo (2012)
  • Author(s): Sato K, Misawa N, Satou Y, Matsuoka M, Ito M, Koyanagi Y
  • Organizer: 37th Retroviruses Meeting
  • Place of Presentation: Cold Spring Harbor (米国)
  • Year and Date: 2012-05-22
• [Presentation] DNA damage induces illegitimate integration of HIV-1 in the presence of integrase inhibitor, leading to produce a viral reservoir (2012)
  • Author(s): Ebina H, Kanemura Y, Suzuki Y, Urata K, Misawa N, Koyanagi Y
  • Organizer: 37th Retroviruses Meeting Cold Spring Harbor, poster, New York
  • Place of Presentation: Cold Spring Harbor (米国)
  • Year and Date: 2012-05-22
• [Presentation] Overview of infection model of humanized mice (2012)
  • Author(s): 小柳義夫
  • Organizer: 1st Samsung Humanized Mice Symposium(招待講演)
  • Place of Presentation: ソウル(韓国)
  • Year and Date: 2012-04-13
• [Presentation] Biochemical characterization of the HIV- 1 restriction factor SAMHD1 (2012)
  • Author(s): Gee P, Okamoto S, Kanemura Y, Ebina H,Koyanagi Y
  • Organizer: 第19回 Conference on Retroviruses and Opportunistic Infections
  • Place of Presentation: シアトル(米国)
  • Year and Date: 2012-03-06
• [Presentation] Induction of immune activation by the depletion of regulatory CD4+ T cell during acute HIV-1 infection in humanized mouse model (2012)
  • Author(s): Sato K, Misawa N, Satou ., Matsuoka M, Ito M, Koyanagi Y
  • Organizer: 19th Conference on Retroviruses and Opportunistic Infections
  • Place of Presentation: シアトル(米国)
  • Year and Date: 2012-03-05
• [Presentation] Overview of infection model of humanized mice (2012)
  • Author(s): Koyanagi Y.
  • Organizer: 1st Samsung Humanized Mice Symposium
  • Place of Presentation: Seoul (Korea)
  • Invited
• [Presentation] DNA damage induces illegitimate integration of HIV-1 in the presence of integrase inhibitor, leading to produce a viral reservoir (2012)
  • Author(s): Ebina H., Kanemura Y., Suzuki Y., Urata K., Misawa N., Koyanagi Y.
  • Organizer: 37th Retroviruses Meeting
  • Place of Presentation: Cold Spring Harbor (米国New York)
• [Presentation] Positive contribution of HIV-1 Vpu for viral propagation in vivo (2012)
  • Author(s): Sato K., Misawa N., Satou Y., Matsuoka M., Ito M., Koyanagi Y.
  • Organizer: 37th Retroviruses Meeting
  • Place of Presentation: Cold Spring Harbor (米国New York)
• [Presentation] レトロウイルス感染におけるエフェクター分子 (2012)
  • Author(s): 小柳義夫
  • Organizer: 北海道大学遺伝子制御研究所研究集会「感染と癌 -感染癌のエフェクター分子とその標的-」
  • Place of Presentation: 北海道大学医学部学友会館(札幌)
  • Invited
• [Presentation] Biochemical characterization of the HIV-1 restriction factor SAMHD1 (2012)
  • Author(s): Gee P, Okamoto S, Kanemura Y, Ebina H, Koyanagi Y
  • Organizer: 第19回Conference on Retroviruses and Opportunistic infections
  • Place of Presentation: シアトル（米国）
• [Presentation] (2011)
  • Author(s): Gee P, Kanemura Y, Ebina H, Koyanagi Y
  • Organizer: 第12回熊本エイズセミナー
  • Place of Presentation: 阿蘇リゾート グランヴィリオ ホテル(阿蘇市)
  • Year and Date: 2011-10-20
• [Remarks]
  • URL: http://www.virus.kyoto-u.ac.jp/Lab/KoyanagiHP/saito/TOP.html
• [Remarks] ウイルス研究所 年報 Volume 54 2011
  • URL: http://www.virus.kyoto-u.ac.jp/about/data2011/AR2011_full.pdf
• [Remarks]
  • URL: http://www.virus.kyoto-u.ac.jp/Lab/KoyanagiHP/rekucha/2011_Annual_report.html