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

• Project/Area Number: 07277103
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• 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): 島田 隆 日本医科大, 医学部, 教授 (20125074) ; 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)
• Project Period (FY): 1997
• Project Status: Completed (Fiscal Year 1997)
• Budget Amount: ¥137,400,000 (Direct Cost: ¥137,400,000); Fiscal Year 1997: ¥46,800,000 (Direct Cost: ¥46,800,000); Fiscal Year 1996: ¥46,800,000 (Direct Cost: ¥46,800,000); Fiscal Year 1995: ¥43,800,000 (Direct Cost: ¥43,800,000)
• Keywords: HIV-1 / エイズ / ケモカイン / コレセプター / 阻害剤 / アンチセンス / 遺伝子治療 / Tat / HIV / V3 loop / 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 / V3loop

Research Abstract

ケモカイン、コレセプターおよびその阻害剤
Revの新規主要コファクターとしてhumanCRM1を同定した。またコファクターとして既報のRip/RABとの関係を調べることにより、Rev,CRM,Ripの3者(または4者)が複合体を形成していることを示唆した(志田)。アミノ酸18個よりなる低分子ペプチドT22がT細胞株指向性HIV-1のコレセプターであるCXCR4に特異的に吸着することにより、HIV-1の細胞への侵入を阻害することがわかった(山本)。
アンチセンス戦略と遺伝子治療
セカンドレセプターCCR5遺伝子を標的にしたアンチセンス核酸分子を構築し、その発現を阻害することで実際にウイルス感染を防ぐことができる可能性を示唆した(高久)。効果の高い抗HIV-1リボザイム発現系を構築した。転写後のリボザイムの高次構造を十分考慮して発現系を設計することの重要性が明らかとなった(多比良)。高力価のT細胞やマクロファージ特異的HIVベクターを作製し、高率で遺伝子を導入できることを示した(島田)。
病態、シグナル伝達およびHIVの転写調節
HIV蛋白のTatがIL-12産生を低下させることを見い出し、これによってもHIV感染者の免疫能が低下する可能性を示した(伊藤)。HIV感染の病態の解析と治療の開発のため免疫不全の進行要因としてのクワシスピーシスの解析(ウイルス側の要因)と免疫反応(宿主側の要因)の研究を行った(松下)。

Research Products

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