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Establishment of Rev based anti-HIV therapy.

建立基于 Rev 的抗 HIV 疗法。

基本信息

批准号：
17591037
负责人：
KODAMA Eiichi
金额：
$ 2.18万
依托单位：
Kyoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17591037/
关键词：
human immunodeficiency virus Rev anti-viral agent peptide resistance HIV 治療

项目摘要

Even under highly active anti-retroviral therapy using extensive combination of inhibitors to reverse transcriptase and/or protease, eradication of human immunodeficiency virus (HIV) remains to be achieved. Thus, development of new inhibitors that block new targets as well as reverse transcriptase or protease is urgently required. In this project, the principal investigator focuses on a viral accessory protein, Rev that is essential for HIV replication and has developed peptide based Rev inhibitors.The investigator found that a peptide containing 10 to 63 amino acids of Rev transduced cells were resistant to HIV infection, suggesting that the region contains an HIV inhibitory peptide sequence. To identify the region, expression vectors containing peptide sequences in various size and region of Rev 10 to 63 were constructed. Among them, a peptide containing arginine rich 34 to 50 amino acid sequence showed inhibitory effect. Addition of four alanines that stabilize α-helical structure enhances the inhibitory effect. Human T-cell leukemia virus Rex, a homolog of Rev also has arginine rich domain. This region also showed inhibitory effect to HIV infection. Synthetic peptides also block HIV infections through its binding to CXCR4, not through suppression of Rev function, indicating that enhancement of peptide penetration efficiency into cells is needed. Further study is needed to develop clinically useful Rev inhibitors.

即使在使用逆转录酶和/或蛋白酶抑制剂的广泛组合的高活性抗逆转录病毒疗法下，仍有待实现人类免疫缺陷病毒（HIV）的根除。因此，迫切需要开发阻断新靶标以及逆转录酶或蛋白酶的新抑制剂。本项目主要研究HIV复制所必需的病毒辅助蛋白Rev，并开发了基于肽的Rev抑制剂。研究者发现Rev转导细胞的一个含有10至63个氨基酸的肽对HIV感染具有抗性，这表明该区域含有HIV抑制肽序列。为了鉴定该区域，构建了含有不同大小的肽序列和Rev 10至63区域的表达载体。其中，含有富含精氨酸的34至50个氨基酸序列的肽显示抑制作用。添加稳定α-螺旋结构的四种丙氨酸增强了抑制作用。人T细胞白血病病毒雷克斯是Rev的同源物，也具有富含精氨酸的结构域。该区域对HIV感染也有抑制作用。合成肽也通过其与CXCR 4的结合而不是通过抑制Rev功能来阻断HIV感染，这表明需要增强肽渗透到细胞中的效率。需要进一步的研究来开发临床上有用的Rev抑制剂。

项目成果

期刊论文数量（18）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

A novel colorimetric assay for CXCR4 and CCR5 tropic human immunodeficiency viruses

CXCR4 和 CCR5 热带人类免疫缺陷病毒的新型比色测定

DOI：
发表时间：
2006
期刊：
Antivir Chem Chemother 17
影响因子：
0
作者：
Suzuki A;Yamada R;Ohtake-Yamanaka M;Okazaki Y;Sawada T;Yamamoto K.;Kajiwara K.
通讯作者：
Kajiwara K.

RNase S complex bearing arginine-rich peptide and anti-HIV activity.

RNase S 复合物具有富含精氨酸的肽和抗 HIV 活性。

DOI：
发表时间：
2004
期刊：
J Mol Recognit 18
影响因子：
0
作者：
Nakata S;Matsumura I;Tanaka H;Ezoe S;Satoh Y;Ishikawa J;Era T;Kanakura Y.;Nameki D;Kitano K;Kohgo S;Hachiya A;Masuda N;Futaki S
通讯作者：
Futaki S

Halogenated thymidine analogs restore the expression of silenced genes without demethylation.

卤化胸苷类似物可恢复沉默基因的表达而不发生去甲基化。

DOI：
发表时间：
2005
期刊：
Cancer Res 65
影响因子：
0
作者：
Zhao T;Yasunaga J-I;Satou Y;Nakao M;Takahashi M;Fujii M;Matsuoka M.;Suemori K;Shimura K.;Mitchell MS.;Yoshida M.;Hino S.;Tajima S.;Satou Y.;Taniguchi Y.;Doi K.;Fan J.
通讯作者：
Fan J.

Novel HIV-1 integrase inhibitors derived from quinolone antibiotics