1997 年度実績報告書

エイズの病態と制御に関する基礎研究エイズの動物モデル

研究課題

研究課題/領域番号	07277106
研究機関	京都大学
研究代表者	速水正憲京都大学, ウイルス研究所, 教授 (40072946)
研究分担者	岩倉洋一郎東京大学, 医科学研究所, 教授 (10089120) 田中勇悦北里大学, 理学部, 助教授 (30163588) 木梨達雄東京大学, 医科学研究所, 助手 (30202039) 見上彪東京大学, 農学部, 教授 (20091506) 向井鐐三郎国立感染症研究所, 筑波支所, 主任研究官 (90133040)
キーワード	サル免疫不全ウイルス / ネコ免疫不全ウイルス / キメラウイルス / トランスジェニックマウス / スキッドマウス / ヒト免疫不全ウイルス / マウスエイズ / 後天性免疫不全症
研究概要	HIVの感染・発症機序の解明さらに治療薬・ワクチン開発の為に以下の動物モデルを用いた研究を実施した。 1.サル (1)サル免疫不全ウイルス(SIV):SIVの経膣感染の際にウイルス集団が制限されるが、必ずしもマクロファージ指向性SIVが感染しなかった (速水)。6-C1-ddGを感染初期と中期に投与したところ、ウイルス量の低下や症状の軽減が認められた (向井)。 (2)HIV-1/SIVキメラウイルス (SHIV):IIIb型のHIV-1envをもつSHIVの免疫ザルでは、MN型に対する中和抗体も誘導され、その攻撃接種に抵抗性を示した。また種々の性状をもつHIV-1envを組込んだSHIVは、サル細胞でも同様な性状を示した (速水) 2.ネコネコ免疫不全ウイルス(FIV)の経粘膜感染系を確立し、さらにAP-1結合部位欠損変位株が経粘膜感染防御ワクチンとなりうる可能性を示した。また粘膜免疫を誘導できるネコヘルペスウイルスI型をベクターとしたFIVのGag,Envを発現するウイルスを作出した (見上)。 3.マウス (1)スキッドマウス:hu-PBL-スキッドマウスにおいて、nefのacidic domain, serin kinase association domainがHIV-1の増殖と病原性に関与することを示した (田中)。 (2)トランスジェニックマウス:ヒトCD4とCXCR4,CCR3,CCR5を共発現するマウスを作成した。感染初期は再現できたが、プロウイルス化の効率が低下し、子孫ウイルスの産生は認められなかった。またvpr遺伝子導入マウスで、胸腺細胞のアポトーシスの亢進とその萎縮及び末梢T細胞の減少が認められた (岩倉)。 (3)マウス・エイズ:ブルトン型チロシンキナーゼ (Btk) に1アミノ酸置換をもつ変異Btkをもつマウスでは、発症の遅延が認められた (木梨)。

研究成果

(38件)

すべてその他

すべて文献書誌 (38件)

[文献書誌] Kuwata T.,Hayami,M.et al.: "The rapid spread of recombinants during a natural in vitro infection with two Human Immunodeficiency Virus type 1 strains." J.Virol. 71. 7088-7091 (1997)
[文献書誌] Enose,Y.,Hayami,M.et al.: "Restriction of viral population by Intravaginal Infection of simian Immunodeficiency viruses in Macaque Monkeys." Arch.Virol.142. 37-51 (1997)
[文献書誌] Murayama,Y.,Mukai,R.,Hayami,M.et al.: "CD4 and CD8 expressions in African green monkey helper T lymphocytes : Implication for resistance to SIV infection." International Immunology. 9(6). 843 (1997)
[文献書誌] Chen,J.,Hayami,M.et al.: "Replication of HIV-1,SIVmac and Chimeric HIV-1/SIVmac Viruses having env genes derived from macrophage-tropic viruses : an indication od different mechanisms of macrophage-tropism in human and monkey cells." J.Gen.Viol.(in press).
[文献書誌] Ido,E.,Hayami,M et al.: "Infection of an HIV-1/SIVmac chimeric virus having HIV-1 env to Macaque monkeys via Vaginal Cavity." Microbiol. & Immunol.41(3). 277-280 (1997)
[文献書誌] Igarashi T.,Mukai,R.,Hayami M.et al.: "Protection of monkeys vaccinated with vpr-and/or nef-defective simian immunodeficiency virus strain mac/human immunodeficiency virus type 1 chimeric viruses : a potential candidate live-attenuated human AIDS vaccine." J.Gen.Virol.78. 985-989 (1997)
[文献書誌] Bogers,WH.Hayami,M.et al.: "Comparison of in vitro and in vivo infectivity of different clade B HIV-1 envelope chimeric simian/human immunodeficiency virus in Macaca mulatta." Virology. 236. 110 (1997)
[文献書誌] Iida,T.,Hayami,M.et al.: "Fas antigen expression and apoptosis of lymphocytes in macaques infected with simian immunodeficiency virus strain mac" Arch.of Virol.(in press).
[文献書誌] Isaka,Y.,Hayami,M.et al.: "Construction of the chimeric virus clone of simian immunodeficiency virus possessing the sensitive to nonnucleoside reverse transcriptase inhibitor." Microbiol. & Imml.(in press).
[文献書誌] Haga,T.,Hayami,M.et al.: "A new approach to AIDS research and prevention : The use of gene-mutated HIV-1/SIV chimeric viruses for anti-HIV-1 live attenuated vaccines." Microbiol. & lmmunol.(in press).
[文献書誌] Hayami,M.et al.: "Gene-mutated HIV-1/SIV chimeric viruses as AIDS live attenuated vaccines for potential human use." Leukemia. (in press).
[文献書誌] Fuji,Y.,Mukai,R.et al.: "Efficacy of 6-chloro-2',3'-dideoxy guanosine (6-Cl-ddG) on an ARC/AIDS rhesus macaque (Macaca mulatta) infected with simian immuno-deficiency virus" Exp.Anim.46. 83-87 (1997)
[文献書誌] Otani I.,Mukai,R., et al.: "Effects of 6-chloro-2',3'-dideoxy guanosine (6-CI-ddG) in surface lymph nodes of rhesus momkeys (Macaca mulatta) chronically infected with simian immuno deficiency virus (SIVmac239)." J.Vet.Med.Sci.59. 891-896 (1997)
[文献書誌] Fuji,Y.,Mukai,R., et al.: "Efficacy of 6-chloro-2',3'-dideoxy guanosine (6-CI-ddG) on Rhesus macaque chronically infected with simian immuno deficiency virus (SIVmac239)." J.Acquir.Immune.Defic.Syndr.Hum.Retrovirol.16. 313-317 (1997)
[文献書誌] Fuji,Y.,Mukai,R., et al.: "Antiviral effects of 6-chloro-2',3'-dideoxy guanosine (6-Cl-ddG) in rhesus monkeys acutely infected with SIV" Antiviral Chem. & Chemother. 9. 85-92 (1998)
[文献書誌] Shimojima,M.,Mikami,T., et al.: "Generation of monoclonal antibodies against a feline CD antigen (CD4) expressed by a recombinant baculovirus." J.Vet.Med.Sci.59. 467-469 (1997)
[文献書誌] Inada,G.,Mikami,T., et al.: "Phylogenetic analysis of feline immunodeficiency virus isolated from cats in Taiwan." Arch.Virol.149. 1459-1467 (1997)
[文献書誌] Yamamoto,H.,Nikami,T., et al.: "Immunological and histological disorders in cats experimentally infected with feline immunodeficiency virus subtype B (TM2 strain)." Vet Microbiol.57. 313-324 (1997)
[文献書誌] Ikeda,Y.,Mikami,T., et al.: "The effects of treatment with chemical agents or infection with feline viruses on protein-binding properties of the feline immunodeficiency virus long terminal repeat." Virus Res.51. 203-212 (1997)
[文献書誌] Ikeda,Y.,Mikami,T., et al.: "Protein-binding properties of the putative AP-1 and ATF sequences in the feline immunodeficiency virus long terminal repeat." J.Gen.Virol.78. 95-99 (1997)
[文献書誌] Shimojima,M.,Mikami,T., et al.: "Expansion of CD8α+β-cells in cats infected with feline immunodeficiency virus" J.Gen.Virol.78. 91-94 (1997)
[文献書誌] Inoshima,Y.,Mikami,T., et al.: "Cross virus neutralizing antibodies against feline immunodeficiency virus genotypes A,B,C,D and E." Arch.Virol.(in press)
[文献書誌] Shimojima,M.,Mikami,T., et al.: "Characterization of Anti-feline CD8 monoclonal antibodies." Vet Immunol.Immunopathol.(in press).
[文献書誌] Inoshima,Y.,Mikami,T., et al.: "in vivo functions of the auxiliary genes and reguratory elements of feline immunodeficiency virus." Vet.Microbiol.(in press).
[文献書誌] Inoshima,Y.,Mikami,T., et al.: "The roles of vif and ORF-A genes and AP-1 binding site in in vivo replication of feline immunodeficiency virus." Arch.Virol.(in press).
[文献書誌] Kohmoto,K.,Mikami,T., et al.: "Eight-year observation and comparative study of specific pathgen-free cats experimentally infected with feline immunodeficiency virus (FIV) subtypes A and B : terminal acquired immunodeficiency syndrome in a cat infected with FIV petaluma strain." J.Vet.Med.Sci.(in press).
[文献書誌] Sato,E.,Mikami,T., et al.: "Construction of a recombinat feline herpesvirus type 1 expressing Gag precursor protein of feline immunodeficiency virus." Arch.Virol.(in press).
[文献書誌] Tomonaga,K.,Mikami,T., et al.: "Characterization of an integrase mutant of feline immunodeficiency virus" Arch.Virol.(in press).
[文献書誌] Hano,T.,Kinashi,T., et al.: "IL-4 induces homotypic aggregation of human culture mast cells by promoting LFA-1/ICAM-1 adhesion molecules." Blood. 89. 3296-3302 (1997)
[文献書誌] Kawano,Y.,Tanaka,Y., et al.: "Mutational analysis of HIV-1 accessory genes : Requirement of a site in the nefgene for HIV-1 replication in activated CD4_+ T cells in vitro and in vivo." Journal of Virology. 71. 8456-8466 (1997)
[文献書誌] Koyanagi,Y.,Tanaka,Y., et al.: "Primary human immunodeficiency virus type 1 viremia and central nervous system invasion in a novel hu-PBL-immunodeficient mouse strain." Journal of Virology. 71. 2417-2424 (1997)
[文献書誌] Tanaka,Y., et al.: "Productive and lytic infection of human CD4_+type 1 helper T cells with macrophage-tropic human immunodeficiency virus type 1." Journal of Virology. 71. 465-470 (1997)
[文献書誌] Asano,M.,Iwakura,Y.et al.: "Growth retardation and early death of b-1,4-galactosyltransferase knockout mice with augmented proliferation and abnormal differentiationof epithelial cells." EMBO J.16. 1850-1857 (1997)
[文献書誌] Tagawa,Y.,Iwakura,Y.et al.: "Suppression of Concanavalin A induced hepatitis in IFN-g-/-,but not in TNF-a-/-,mice : role for IFN-g in activating apoptosis of hepatocytes." J.Immunol.159. 1418-1428 (1997)
[文献書誌] Ozaki,H.,Iwakura,Y.et al.: "TNF-a,but not IL-1,II-6,or IFN-g is the maior mediator of LPS-induced HIV.activation in mice transgenic for HIV" J.Interferon Cytokine Res.17. S105 (1997)
[文献書誌] Yoshimoto,T.,Iwakura,Y.et al.: "Interleukin 18 together with interleukin 12 inhibits IgE production by induction of interferon-g production from activated B cells." Proc.Natl.Acad.Sci.USA. 94. 3948-3953 (1997)
[文献書誌] Kishi,S.,Iwakura,Y.et al.: "Resistance to Fas-mediated apoptosis of peripheral T cells in human T lymphocyte virus typel (HTLV-1) transgenic mice with autoimmune arthropathy." J.Exp.Med.186. 57-64 (1997)
[文献書誌] Hayami,M.et al.: "SIV/HIV-1 chimeric viruses having HIV-1 env gene : a new animal model and a candidate for attenuated live vaccine." Leukemia,vol.11 : 95-97,ed.Ikawa,Y.,STOCKTON,UK, 95-97 (1997)

1997 年度 実績報告書

エイズの病態と制御に関する基礎研究 エイズの動物モデル

研究代表者

速水 正憲 京都大学, ウイルス研究所, 教授 (40072946)

研究成果

[文献書誌] Kuwata T.,Hayami,M.et al.: "The rapid spread of recombinants during a natural in vitro infection with two Human Immunodeficiency Virus type 1 strains." J.Virol. 71. 7088-7091 (1997)

[文献書誌] Enose,Y.,Hayami,M.et al.: "Restriction of viral population by Intravaginal Infection of simian Immunodeficiency viruses in Macaque Monkeys." Arch.Virol.142. 37-51 (1997)

[文献書誌] Murayama,Y.,Mukai,R.,Hayami,M.et al.: "CD4 and CD8 expressions in African green monkey helper T lymphocytes : Implication for resistance to SIV infection." International Immunology. 9(6). 843 (1997)

[文献書誌] Chen,J.,Hayami,M.et al.: "Replication of HIV-1,SIVmac and Chimeric HIV-1/SIVmac Viruses having env genes derived from macrophage-tropic viruses : an indication od different mechanisms of macrophage-tropism in human and monkey cells." J.Gen.Viol.(in press).

[文献書誌] Ido,E.,Hayami,M et al.: "Infection of an HIV-1/SIVmac chimeric virus having HIV-1 env to Macaque monkeys via Vaginal Cavity." Microbiol. & Immunol.41(3). 277-280 (1997)

[文献書誌] Bogers,WH.Hayami,M.et al.: "Comparison of in vitro and in vivo infectivity of different clade B HIV-1 envelope chimeric simian/human immunodeficiency virus in Macaca mulatta." Virology. 236. 110 (1997)

[文献書誌] Iida,T.,Hayami,M.et al.: "Fas antigen expression and apoptosis of lymphocytes in macaques infected with simian immunodeficiency virus strain mac" Arch.of Virol.(in press).

[文献書誌] Isaka,Y.,Hayami,M.et al.: "Construction of the chimeric virus clone of simian immunodeficiency virus possessing the sensitive to nonnucleoside reverse transcriptase inhibitor." Microbiol. & Imml.(in press).

[文献書誌] Haga,T.,Hayami,M.et al.: "A new approach to AIDS research and prevention : The use of gene-mutated HIV-1/SIV chimeric viruses for anti-HIV-1 live attenuated vaccines." Microbiol. & lmmunol.(in press).

[文献書誌] Hayami,M.et al.: "Gene-mutated HIV-1/SIV chimeric viruses as AIDS live attenuated vaccines for potential human use." Leukemia. (in press).

[文献書誌] Fuji,Y.,Mukai,R.et al.: "Efficacy of 6-chloro-2',3'-dideoxy guanosine (6-Cl-ddG) on an ARC/AIDS rhesus macaque (Macaca mulatta) infected with simian immuno-deficiency virus" Exp.Anim.46. 83-87 (1997)

[文献書誌] Otani I.,Mukai,R., et al.: "Effects of 6-chloro-2',3'-dideoxy guanosine (6-CI-ddG) in surface lymph nodes of rhesus momkeys (Macaca mulatta) chronically infected with simian immuno deficiency virus (SIVmac239)." J.Vet.Med.Sci.59. 891-896 (1997)

[文献書誌] Fuji,Y.,Mukai,R., et al.: "Efficacy of 6-chloro-2',3'-dideoxy guanosine (6-CI-ddG) on Rhesus macaque chronically infected with simian immuno deficiency virus (SIVmac239)." J.Acquir.Immune.Defic.Syndr.Hum.Retrovirol.16. 313-317 (1997)

[文献書誌] Fuji,Y.,Mukai,R., et al.: "Antiviral effects of 6-chloro-2',3'-dideoxy guanosine (6-Cl-ddG) in rhesus monkeys acutely infected with SIV" Antiviral Chem. & Chemother. 9. 85-92 (1998)

[文献書誌] Shimojima,M.,Mikami,T., et al.: "Generation of monoclonal antibodies against a feline CD antigen (CD4) expressed by a recombinant baculovirus." J.Vet.Med.Sci.59. 467-469 (1997)

[文献書誌] Inada,G.,Mikami,T., et al.: "Phylogenetic analysis of feline immunodeficiency virus isolated from cats in Taiwan." Arch.Virol.149. 1459-1467 (1997)

[文献書誌] Yamamoto,H.,Nikami,T., et al.: "Immunological and histological disorders in cats experimentally infected with feline immunodeficiency virus subtype B (TM2 strain)." Vet Microbiol.57. 313-324 (1997)

[文献書誌] Ikeda,Y.,Mikami,T., et al.: "The effects of treatment with chemical agents or infection with feline viruses on protein-binding properties of the feline immunodeficiency virus long terminal repeat." Virus Res.51. 203-212 (1997)

[文献書誌] Ikeda,Y.,Mikami,T., et al.: "Protein-binding properties of the putative AP-1 and ATF sequences in the feline immunodeficiency virus long terminal repeat." J.Gen.Virol.78. 95-99 (1997)

[文献書誌] Shimojima,M.,Mikami,T., et al.: "Expansion of CD8α+β-cells in cats infected with feline immunodeficiency virus" J.Gen.Virol.78. 91-94 (1997)

[文献書誌] Inoshima,Y.,Mikami,T., et al.: "Cross virus neutralizing antibodies against feline immunodeficiency virus genotypes A,B,C,D and E." Arch.Virol.(in press)

[文献書誌] Shimojima,M.,Mikami,T., et al.: "Characterization of Anti-feline CD8 monoclonal antibodies." Vet Immunol.Immunopathol.(in press).

[文献書誌] Inoshima,Y.,Mikami,T., et al.: "in vivo functions of the auxiliary genes and reguratory elements of feline immunodeficiency virus." Vet.Microbiol.(in press).

[文献書誌] Inoshima,Y.,Mikami,T., et al.: "The roles of vif and ORF-A genes and AP-1 binding site in in vivo replication of feline immunodeficiency virus." Arch.Virol.(in press).

[文献書誌] Sato,E.,Mikami,T., et al.: "Construction of a recombinat feline herpesvirus type 1 expressing Gag precursor protein of feline immunodeficiency virus." Arch.Virol.(in press).

[文献書誌] Tomonaga,K.,Mikami,T., et al.: "Characterization of an integrase mutant of feline immunodeficiency virus" Arch.Virol.(in press).

[文献書誌] Hano,T.,Kinashi,T., et al.: "IL-4 induces homotypic aggregation of human culture mast cells by promoting LFA-1/ICAM-1 adhesion molecules." Blood. 89. 3296-3302 (1997)

[文献書誌] Kawano,Y.,Tanaka,Y., et al.: "Mutational analysis of HIV-1 accessory genes : Requirement of a site in the nefgene for HIV-1 replication in activated CD4_+ T cells in vitro and in vivo." Journal of Virology. 71. 8456-8466 (1997)

[文献書誌] Koyanagi,Y.,Tanaka,Y., et al.: "Primary human immunodeficiency virus type 1 viremia and central nervous system invasion in a novel hu-PBL-immunodeficient mouse strain." Journal of Virology. 71. 2417-2424 (1997)

[文献書誌] Tanaka,Y., et al.: "Productive and lytic infection of human CD4_+type 1 helper T cells with macrophage-tropic human immunodeficiency virus type 1." Journal of Virology. 71. 465-470 (1997)

[文献書誌] Asano,M.,Iwakura,Y.et al.: "Growth retardation and early death of b-1,4-galactosyltransferase knockout mice with augmented proliferation and abnormal differentiationof epithelial cells." EMBO J.16. 1850-1857 (1997)

[文献書誌] Tagawa,Y.,Iwakura,Y.et al.: "Suppression of Concanavalin A induced hepatitis in IFN-g-/-,but not in TNF-a-/-,mice : role for IFN-g in activating apoptosis of hepatocytes." J.Immunol.159. 1418-1428 (1997)

[文献書誌] Ozaki,H.,Iwakura,Y.et al.: "TNF-a,but not IL-1,II-6,or IFN-g is the maior mediator of LPS-induced HIV.activation in mice transgenic for HIV" J.Interferon Cytokine Res.17. S105 (1997)

[文献書誌] Yoshimoto,T.,Iwakura,Y.et al.: "Interleukin 18 together with interleukin 12 inhibits IgE production by induction of interferon-g production from activated B cells." Proc.Natl.Acad.Sci.USA. 94. 3948-3953 (1997)

[文献書誌] Kishi,S.,Iwakura,Y.et al.: "Resistance to Fas-mediated apoptosis of peripheral T cells in human T lymphocyte virus typel (HTLV-1) transgenic mice with autoimmune arthropathy." J.Exp.Med.186. 57-64 (1997)

[文献書誌] Hayami,M.et al.: "SIV/HIV-1 chimeric viruses having HIV-1 env gene : a new animal model and a candidate for attenuated live vaccine." Leukemia,vol.11 : 95-97,ed.Ikawa,Y.,STOCKTON,UK, 95-97 (1997)

1997 年度実績報告書

エイズの病態と制御に関する基礎研究エイズの動物モデル

速水正憲京都大学, ウイルス研究所, 教授 (40072946)