Study on in vivo function of APOBEC3 and its effect on pathophysiology of HIV-1 infection

• Project/Area Number: 23390110
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Virology
• Research Institution: Kyoto University
• Principal Investigator: TAKAORI AKIFUMI 京都大学, 医学(系)研究科(研究院), 教授 (20324626)
• Co-Investigator(Renkei-kenkyūsha): 小柳 義夫 京都大学, ウイルス研究所 (80215417)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥20,150,000 (Direct Cost: ¥15,500,000、Indirect Cost: ¥4,650,000); Fiscal Year 2013: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2012: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2011: ¥11,570,000 (Direct Cost: ¥8,900,000、Indirect Cost: ¥2,670,000)
• Keywords: 個体 / 遺伝子 / ウイルス / 進化 / 宿主因子 / 内在性免疫 / 変異 / ゲノム / 感染症 / 免疫 / 感染防御

Research Abstract

1. Analysis on APOBEC3B SNPs and HIV-1 replication; we demonstrate that there is no significant correlation between APOBEC3B deletion phenotype and progression of HIV-1 infection.
2. In vivo analysis on HIV replication in SCID-hu mouse model; we analyzed the replication of HIV-1 and the accumulation of mutations in vivo. We show that APOBEC3G has a potent anti-HIV-1 activity in vivo, whereas APOBEC3F contribute to viral evolution.

Research Products

• [Journal Article] Uric acid induces NADPH oxidase-independent neutrophil extracellular trap formation (2014)
  • Author(s): Arai Y, Nishinaka Y, Arai T, Morita M, Mizugishi K, Adachi S, Takaori-Kondo A, Watanabe T, Yamashita K
  • Journal Title: Biochem Biophys Res Commun Volume: 443(2) Pages: 556-61
• [Journal Article] Quantitative analysis of location- and sequence-dependent deamination by APOBEC3G using real-time NMR spectroscopy (2014)
  • Author(s): Furukawa A, Sugase K, Morishita R, Nagata T, Kodaki T, Takaori-Kondo A, Ryo A, Katahira M
  • Journal Title: Angew Chem Int Ed Engl Volume: 53(9) Pages: 2349-52
• [Journal Article] Lack of Association between Intact/Deletion Polymorphisms of the APOBEC3B Gene and HIV-1 Risk (2014)
  • Author(s): Imahashi M, Izumi T, Watanabe D, Imamura J, Matsuoka K, Ode H, Masaoka T, Sato K, Kaneko N, Ichikawa S, Koyanagi Y, Takaori-Kondo A, Utsumi M, Yokomaku Y, Shirasaka T, Sugiura W, Iwatani Y, Naoe T
  • Journal Title: PLOS ONE Volume: 9(3)
• [Journal Article] Defining HIV-1 Vif residues that interact with CBFbeta by site-directed mutagenesis (2014)
  • Author(s): Matsui Y, Shindo K, Nagata K, Io K, Tada K, Iwai F, Kobayashi M, Kadowaki N, Harris RS, Takaori-Kondo A
  • Journal Title: Virology Volume: 449 Pages: 82-7
• [Journal Article] Senescence-inducing stress promotes proteolysis of phosphoglycerate mutase via ubiquitin ligase Mdm2 (2014)
  • Author(s): Mikawa T, Maruyama T, Okamoto K, Nakagama H, Lleonart ME, Tsusaka T, Hori K, Murakami I, Izumi T, Takaori-Kondo A, Yokode M, Peters G, Beach D, Kondoh H
  • Journal Title: J Cell Biol Volume: 204(5) Pages: 729-45
• [Journal Article] Antitumor effects of bevacizumab in a microenvironment-dependent human adult T-cell leukemia/lymphoma mouse model (2014)
  • Author(s): Mori F, Ishida T, Ito A, Sato F, Masaki A, Narita T, Suzuki S, Yamada T, Takino H, Ri M, Kusumoto S, Komatsu H, Hishizawa M, Imada K, Takaori-Kondo A, Niimi A, Ueda R, Inagaki H, Iida S
  • Journal Title: Eur J Haematol Volume: 92(3) Pages: 219-28
• [Journal Article] CKIP-1 is an intrinsic negative regulator of T-cell activation through an interaction with CARMA1 (2014)
  • Author(s): Sakamoto T, Kobayashi M, Tada K, Shinohara M, Io K, Nagata K, Iwai F, Takiuchi Y, Arai Y, Yamashita K, Shindo K, Kadowaki N, Koyanagi Y, Takaori-Kondo A
  • Journal Title: PLOS ONE Volume: 9(1)
• [Journal Article] Defining HIV-1 Vif residues that interact with CBF by site-directed mutagenesis. (2014)
  • Author(s): Matsui Y, Shindo K, Nagata K, Io K, Tada K, Iwai F, Kobayashi M, Kadowaki N, Harris R, Takaori-Kondo A
  • Journal Title: Virology Volume: 449 Pages: 82-87
  • DOI: 10.1016/j.virol.2013.11.004
  • Peer Reviewed
• [Journal Article] Lack of Association between Intact/Deletion Polymorphisms of the APOBEC3B Gene and HIV-1 Risk. (2014)
  • Author(s): Imahashi M, Izumi T, Watanabe D, Imamura J, Matsuoka K, Ode H, Masaoka T, Sato K, Kaneko N, Ichikawa S, Koyanagi Y, Takaori-Kondo A, Utsumi M, Yokomaku Y, Shirasaka T, Sugiura W, Iwatani Y, Naoe T.
  • Journal Title: PLoS One Volume: 9 Issue: 3 Pages: e92861-e92861
  • DOI: 10.1371/journal.pone.0092861
  • Peer Reviewed
• [Journal Article] Quantitative analysis of location- and sequence-dependent deamination by APOBEC3G using real-time NMR spectroscopy (2014)
  • Author(s): Furukawa, A., Sugase, K., Morishita, R., Nagata, T., Kodaki, T., Takaori-Kondo, A., Ryo, A., Katahira, M.
  • Journal Title: Angew. Chem. Int. Ed. Engl. Volume: 53 Issue: 9 Pages: 2349-2352
  • DOI: 10.1002/anie.201309940
  • NAID: 120005647511
  • Peer Reviewed / Open Access
• [Journal Article] CKIP-1 Is an Intrinsic Negative Regulator of T-Cell Activation through an Interaction with CARMA1. (2014)
  • Author(s): Sakamoto T, Kobayashi M, Tada K, Shinohara M, Io K, Nagata K, Iwai F, Takiuchi Y, Arai Y, Yamashita K, Shindo K, Kadowaki N, Koyanagi Y, Takaori-Kondo A
  • Journal Title: PLoS One Volume: 9 Issue: 1 Pages: 1-11
  • DOI: 10.1371/journal.pone.0085762
  • Peer Reviewed
• [Journal Article] Direct binding of Grb2 has an important role in the development of myeloproliferative disease induced by ETV6/FLT3 (2013)
  • Author(s): Chonabayashi K, Hishizawa M, Kawamata S, Nagai Y, Ohno T, Ishikawa T, Uchiyama T, Takaori-Kondo A
  • Journal Title: Leukemia Volume: 27(6) Pages: 1433-6
• [Journal Article] The tyrosine kinase inhibitor dasatinib suppresses cytokine production by plasmacytoid dendritic cells by targeting endosomal transport of CpG DNA (2013)
  • Author(s): Fujita H, Kitawaki T, Sato T, Maeda T, Kamihira S, Takaori-Kondo A, Kadowaki N
  • Journal Title: Eur J Immunol Volume: 43(1) Pages: 93-103
• [Journal Article] Human CD1c+ Myeloid Dendritic Cells Acquire a High Level of Retinoic Acid-Producing Capacity in Response to Vitamin D3 (2013)
  • Author(s): Sato T, Kitawaki T, Fujita H, Iwata M, Iyoda T, Inaba K, Ohteki T, Hasegawa S, Kawada K, Sakai Y, Ikeuchi H, Nakase H, Niwa A, Takaori-Kondo A, Kadowaki N
  • Journal Title: J Immunol Volume: 191(6) Pages: 3152-60
• [Journal Article] Human herpesvirus-6 encephalitis during hematopoietic stem cell transplantation leads to poor prognosis (2013)
  • Author(s): Shimazu Y, Kondo T, Ishikawa T, Yamashita K, Takaori-Kondo A
  • Journal Title: Transpl Infect Dis Volume: 15(2) Pages: 195-201
• [Journal Article] HIV-1 Vif : a guardian of the virus that opens up a new era in the research field of restriction factors (2013)
  • Author(s): Takaori-Kondo A, Shindo K
  • Journal Title: Front Microbiol Volume: 4 Pages: 34-34
  • NAID: 120005244663
• [Journal Article] Human CD1c^+ myeloid dendritic cells acquire a high level of retinoic acid-producing capacity in response to vitamin D_3 (2013)
  • Author(s): Sato T, Kitawaki T, Fujita H, Iwata M, Iyoda T, Inaba K, Ohteki T, Hasegawa S, Kawada K, Sakai Y, Ikeuchi H, Nakase H, Niwa A, Takaori-Kondo A, and Kadowaki N
  • Journal Title: J Immunol Volume: 191(6) Issue: 6 Pages: 3152-3160
  • DOI: 10.4049/jimmunol.1203517
  • Peer Reviewed
• [Journal Article] HIV-1 Vif: a guardian of the virus that opens up a new era in the research field of restriction factors. (2013)
  • Author(s): Takaori-Kondo A
  • Journal Title: Front Microbiol Volume: 4 Pages: 34-34
  • NAID: 120005244663
  • Peer Reviewed
• [Journal Article] NMR study of xenotropic murine leukemia virus-related virus protease in a complex with amprenavir (2012)
  • Author(s): Furukawa A, Okamura H, Morishita R, Matsunaga S, Kobayashi N, Ikegami T, Kodaki T, Takaori-Kondo A, Ryo A, Nagata T, Katahira M
  • Journal Title: Biochem Biophys Res Commun Volume: 425(2) Pages: 284-9
• [Journal Article] Molecular and enzymatic characterization of XMRV protease by a cell-free proteolytic analysis (2012)
  • Author(s): Matsunaga S, Sawasaki T, Ode H, Morishita R, Furukawa A, Sakuma R, Sugiura W, Sato H, Katahira M, Takaori-Kondo A, Yamamoto N, Ryo A
  • Journal Title: J Proteomics Volume: 75(15) Pages: 4863-73
• [Journal Article] APOBEC3B can impair genomic stability by inducing base substitutions in genomic DNA in human cells (2012)
  • Author(s): Shinohara M, Io K, Shindo K, Matsui M, Sakamoto T, Tada K, Kobayashi M, Kadowaki N, Takaori-Kondo A
  • Journal Title: Sci Rep Volume: 2 Pages: 806-806
• [Journal Article] APOBEC3B can impair genomic stability by inducing base substitutions in genomic DNA in human cells. (2012)
  • Author(s): Shinohara M
  • Journal Title: Sci Rep Volume: 2 Issue: 1 Pages: 806-806
  • DOI: 10.1038/srep00806
  • Peer Reviewed
• [Journal Article] NMR study of xenotropic murine leukemia virus-related virus protease in a complex with amprenavir (2012)
  • Author(s): Ayako Furukawa, Hideyasu Okamura, Ryo Morishita, Satoko Matsunaga, Naohiro Kobayashi, Takahisa Ikegami, Tsutomu Kodaki, Akifumi Takaori-Kondo, Ryo Akihide, Takashi Nagata, Masato Katahira
  • Journal Title: Biochem Biophys Res Commun. Volume: 24巻 Issue: 2 Pages: 284-289
  • DOI: 10.1016/j.bbrc.2012.07.083
  • NAID: 120004873605
  • Peer Reviewed
• [Journal Article] Molecular and enzymatic characterization of XMRV protease by a cell-free proteolytic analysis. (2012)
  • Author(s): Matsunaga S
  • Journal Title: J Proteomics Volume: 75 Issue: 15 Pages: 4863-4873
  • DOI: 10.1016/j.jprot.2012.05.047
  • Peer Reviewed
• [Journal Article] A proteasome inhibitor bortezomib suppresses immunostimulatory activity of human plasmacytoid dendritic cells by targeting intracellular (2011)
  • Author(s): Hirai, et al
  • Journal Title: Blood Volume: 117 Pages: 500-9
  • Peer Reviewed
• [Remarks]
  • URL: http://www.kuhp.kyoto-u.ac.jp/~hemonc/
• [Remarks] 京都大学大学院医学研究科 血液・腫瘍内科学
  • URL: http://www.kuhp.kyoto-u.ac.jp/~hemonc/
• [Remarks]
  • URL: http://www.kuhp.kyoto-u.ac.jp/~hemonc/research/hiv.html