Corrections of functional activities of macrophages in infectious diseases using lentivirus vectors.

使用慢病毒载体校正传染病中巨噬细胞的功能活动。

• 批准号: 11557072
• 负责人: HATTORI Toshio
• 金额: $ 8.45万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11557072/
• 关键词: gene therapy; letivirus; vector; macrophages; infectious; レンチウィルス; 偽ウィルス; 平滑筋細胞; レンチウィルスベクタ; VSV-G; 43Ti

Infectious diseases are a major cause of death in developing countries. Diseases such as ATL, AIDS and tuberculosis are still intractable in our country. In these disorders, macrophages play important roles for developing pathological changes. We have attempted to infect lentivirus vectors to infect human smooth muscle cells derived from the pulmonary artery. The lentivirus vectors are pseudotype viruses made of envelopes from X4, R5, X4R5 and VSV. The viruses could infect to corresponding target cells but could not infect to macrophages. To improve the infection to target cells, we have analyzed the conformational changes of gp41. These analyzes showed that human monoclonal antibody reacts with fusogenic structure of gp41, indicating that the structures are immunogenic. We also found that V3 loop peptide could enhance infection of the original viruses. Above studies would be applicable to the development of vectors for macrophages.

传染病是发展中国家的主要死因。ATL、艾滋病和结核病等疾病在我国仍然是棘手的问题。在这些疾病中，巨噬细胞在发生病理变化中起重要作用。我们已经尝试感染慢病毒载体来感染来自肺动脉的人平滑肌细胞。慢病毒载体是由来自X4、R5、X4R5和VSV的包膜制成的假型病毒。病毒能感染相应的靶细胞，但不能感染巨噬细胞。为了提高对靶细胞的感染性，我们分析了gp41的构象变化。这些分析表明，人单克隆抗体与gp41的融合结构反应，表明该结构具有免疫原性。我们还发现V3环肽可以增强原始病毒的感染。上述研究将适用于巨噬细胞载体的开发。

项目成果

Toshio Hattori他3名: "Inhibition of infection of incoming HIV-1 virus by RNA-cleaving DNA enzyme"FEBS Letters. 458. 151-156 (1999)

Toshio Hattori 和其他 3 人：“通过 RNA 切割 DNA 酶抑制传入的 HIV-1 病毒的感染”FEBS Letters 458. 151-156 (1999)。

Taniguchi Y., Zolla-Pazner S., Xu Y., Zhang X., Takeda S., Hattori T.: "A Human Monoclonal Antibody (98-6) Reacts with the Fusogenic Form of gp41"Virology. 273. 333-340 (2000)

Taniguchi Y.、Zolla-Pazner S.、Xu Y.、Zhang X.、Takeda S.、Hattori T.：“人单克隆抗体 (98-6) 与 gp41 的融合形式发生反应”病毒学。

Toshio Hattori他3名: "Inhibition of infection of incoming HIV-1 virus by RNA-cleaving DNA enzyme"FEBS Letter. 458. 151-156 (1999)

Toshio Hattori 和其他 3 人：“通过 RNA 切割 DNA 酶抑制传入的 HIV-1 病毒的感染”FEBS Letter 458. 151-156 (1999)。

Zhang X., Xu Y., Ling H., and Hattori T.: "Inhibition of infection of incoming HIV-1 virus by RNA-cleaving DNA enzyme."FEBS Letters. 458. 151-156 (1999)

张X.、徐Y.、凌H.和服部T.：“通过RNA切割DNA酶抑制传入的HIV-1病毒的感染。”FEBS快报。

Toshio Hattori他7名: "Novel Roles of CpG Oligodeoxynucleotides as a Leader for the Sampling and Presentation of CpG-Tagged Ag by Dendritic Cells"J. Immunol.. 167. 66-74 (2001)

Toshio Hattori 和其他 7 人：“CpG 寡脱氧核苷酸作为树突状细胞采样和呈现 CpG 标签 Ag 的领导者的新角色”J.Immunol.. 167. 66-74 (2001)