1995 Fiscal Year Annual Research Report

エイズの病態と制御に関する基礎研究柱5・感染と病態の制御

Research Project

Project/Area Number	07277103
Research Institution	Tokyo Medical and Dental University
Principal Investigator	山本直樹東京医科歯科大学, 医学部, 教授 (00094053)
Co-Investigator(Kenkyū-buntansha)	伊藤正彦山梨医科大学, 医学部, 教授 (90045740) 松下修三熊本大学, 医学部, 助手 (00199788) 志田壽利京都大学, ウイルス研究所, 助教授 (00144395) 多比良和誠筑波大学, 応用生物化学系, 教授 (10261778) 高久洋千葉工業大学, 工学部, 教授 (50101267)
Keywords	HIV / V3loop / リボザイム / Rev / クワシスピーシス / 中和モノクローナル抗体 / 硫酸アルキルオリゴ糖 / エイズ遺伝子治療
Research Abstract	1.山本)HIVの細胞進入とウイルス増殖に必要な細胞側因子を同定するためにenv蛋白のV3loopと修飾遺伝産物に結合する分子をYeast two hybridで検索し、いくつかの新しい遺伝子を得た。 2.高久)三重鎖を形成することのできるユニークなDNAオリゴマーを見いだした。さらに、このDNAオリゴマーのin vitro系での三重鎖形成能と抗HIV活性を評価すること、および、詳細な作用機序の解明を試みた。 3.多比良)これまでに複数のリボザイム(RZ)を同時に発現させることにより、耐性株の出現を効果的に抑制きるようにした多弾型RZ発現系を開発した。さらに、デコイ機能を付加し、より高い抗HIV効果がみれるどうか調べている。 4.志田)薬剤耐性ウイルスの出現の問題を克服する一つの方法は宿主因子を標的とする薬剤の開発である。エイズ薬開発の基礎としてRevの宿主コファクター、阻害因子の同定と解析を行い、新しい細胞の制御因子考えられるCellular revのCloningを進めている。 5.松下)約半数の症例でHIVクワシスピーシスの増殖が中和モノクローナル抗体と逆転写酵素阻害剤ddIの用により抑制できることを示した。さらに、中和モノクローナル抗体の臨床試験にむけての基礎研究を行いCD4関連分子を用いて、さらに多くの症例でのクワシスピーシスの増殖の抑制を試みた。 6.伊藤)経静脈的に投与した時に高い血中濃度を持続する硫酸アルキルオリゴ糖(DL-110)を発見し、これを告した。さらに、経口投与可能な誘導体(BSL)を合成したので、、その作用機序と臨床有用性について検討中でる。 7.島田)リンパ球あるいは造血幹細胞への遺伝子導入法を開発し、これを使った新しいエイズ遺伝子治療法ストラテジーを確立するための条件検討を行った。また、CD4陽性細胞に特異的に感染できるHIVベクター開発した。

Research Products

(14 results)

All Other

All Publications (14 results)

[Publications] J.Suzuki,et al.: "The association of antibodies against HTLV-1pX-gene mutant products with HTLV-1-associated myelopathy(HAM)/tropical spastic paraparesis(TSP)." J.Infect.Dis.(in press).
[Publications] N.Yamamoto: "The role of cytokines in the acquired immunodeficiency syndrome." Int J Clin Lab Res. 25. 29-34 (1995)
[Publications] T.Hatta,et al.: "Phosphorothioate oligonucleotides block reverse transcription by the RNase H activity associated with the HIV-1 polymerase." Biochem.Biophys.Res.Commun.211. 1041-1046 (1995)
[Publications] K.Hosono,et al.: "Properties of base-pairing in the stem region of hairpin antisense oligonucleotides containing 2'-methoxynucleosides." Biochem.Biophys.Acta. 1244. 339-344 (1995)
[Publications] T.Shimayama,et al.: "Generality of the NUX rule;Kinetic analysis of the results of systematic mutations in the trinucleotide at the cleavage site of hammerhead ribozymes." Biochemistry. 34. 3649-3654 (1995)
[Publications] S.Sawata,et al.: "Kinetic evidence based on solvent isotope effects for the nonexistence of a proton-transfer process in reactions catalyzed by a hammeread ribozyme:Implication to the double-metal-ion mechanism of catalysis." J.Am.Chem.Soc.117. 2357-2358 (1995)
[Publications] Y.Tanaka,et al.: "Induction of antibody responses that neutralize human T-cell leukemia virus type I infection in vitro in vitro and in vivo by peptide immunization." J.Virol.68. 6323-6331 (1994)
[Publications] J.Katahira,et al.: "Effect of translation initiation factor elF-5A on the functioning of human T-cell leukemia virus type I Rex and human immunode ficiency virus Rev inhibited trans dominantly by a Rex mutant deficient in RNA binding." J.Virol.69. 3125-3133 (1995)
[Publications] S.Matsushita,et al.: "Neutralizing monoclonal antobodies against human immunodeficirncy virus type 2gp120." J.Virol.69. 3333-3340 (1995)
[Publications] S.Matsumi,et al.: "Neutralizing monoclonal antibody against an external envelope glycoprotein(gp110)of SIVmac251." AIDS Res.Hum.Retrov.6. 501-508 (1995)
[Publications] H.Shang,et al.: "Suppression of HIV-1 reverse transcriptase activity by culture supernatants of mycoplasmas." Microbiology and Immunology. (in press).
[Publications] H.Nakashima,et al.: "Sulfated alkyl oligosaccharides inhibit human immunodeficiency virus in vitro and provide sustained drug levels in mammals." Antiviral Chemistry & Chemotherapy. 6. 271-280 (1995)
[Publications] T.Shimada,et al.: "Targeted gene transfer into CD4 positive cells by HIV based retrovital vectors." J.Acta Hematologica. (in press).
[Publications] K.Tamayose,et al.: "A new strategy for large scale preparation of high titer recombinant adeno-associated virus(AAV)vectors by using packaging cell lines and sulfonated column." Hum.Gene Thera.(in press).

1995 Fiscal Year Annual Research Report

エイズの病態と制御に関する基礎研究 柱5・感染と病態の制御

Principal Investigator

山本 直樹 東京医科歯科大学, 医学部, 教授 (00094053)

Research Products

[Publications] J.Suzuki,et al.: "The association of antibodies against HTLV-1pX-gene mutant products with HTLV-1-associated myelopathy(HAM)/tropical spastic paraparesis(TSP)." J.Infect.Dis.(in press).

[Publications] N.Yamamoto: "The role of cytokines in the acquired immunodeficiency syndrome." Int J Clin Lab Res. 25. 29-34 (1995)

[Publications] T.Hatta,et al.: "Phosphorothioate oligonucleotides block reverse transcription by the RNase H activity associated with the HIV-1 polymerase." Biochem.Biophys.Res.Commun.211. 1041-1046 (1995)

[Publications] K.Hosono,et al.: "Properties of base-pairing in the stem region of hairpin antisense oligonucleotides containing 2'-methoxynucleosides." Biochem.Biophys.Acta. 1244. 339-344 (1995)

[Publications] T.Shimayama,et al.: "Generality of the NUX rule;Kinetic analysis of the results of systematic mutations in the trinucleotide at the cleavage site of hammerhead ribozymes." Biochemistry. 34. 3649-3654 (1995)

[Publications] S.Sawata,et al.: "Kinetic evidence based on solvent isotope effects for the nonexistence of a proton-transfer process in reactions catalyzed by a hammeread ribozyme:Implication to the double-metal-ion mechanism of catalysis." J.Am.Chem.Soc.117. 2357-2358 (1995)

[Publications] Y.Tanaka,et al.: "Induction of antibody responses that neutralize human T-cell leukemia virus type I infection in vitro in vitro and in vivo by peptide immunization." J.Virol.68. 6323-6331 (1994)

[Publications] J.Katahira,et al.: "Effect of translation initiation factor elF-5A on the functioning of human T-cell leukemia virus type I Rex and human immunode ficiency virus Rev inhibited trans dominantly by a Rex mutant deficient in RNA binding." J.Virol.69. 3125-3133 (1995)

[Publications] S.Matsushita,et al.: "Neutralizing monoclonal antobodies against human immunodeficirncy virus type 2gp120." J.Virol.69. 3333-3340 (1995)

[Publications] S.Matsumi,et al.: "Neutralizing monoclonal antibody against an external envelope glycoprotein(gp110)of SIVmac251." AIDS Res.Hum.Retrov.6. 501-508 (1995)

[Publications] H.Shang,et al.: "Suppression of HIV-1 reverse transcriptase activity by culture supernatants of mycoplasmas." Microbiology and Immunology. (in press).

[Publications] H.Nakashima,et al.: "Sulfated alkyl oligosaccharides inhibit human immunodeficiency virus in vitro and provide sustained drug levels in mammals." Antiviral Chemistry & Chemotherapy. 6. 271-280 (1995)

[Publications] T.Shimada,et al.: "Targeted gene transfer into CD4 positive cells by HIV based retrovital vectors." J.Acta Hematologica. (in press).

[Publications] K.Tamayose,et al.: "A new strategy for large scale preparation of high titer recombinant adeno-associated virus(AAV)vectors by using packaging cell lines and sulfonated column." Hum.Gene Thera.(in press).

エイズの病態と制御に関する基礎研究柱5・感染と病態の制御

山本直樹東京医科歯科大学, 医学部, 教授 (00094053)