Rev 衍生肽通过拮抗 Rev 和共受体 CXCR4 抑制 HIV-1 复制。

Rev-derived peptides inhibit HIV-1 replication by antagonism of Rev and a co-receptor, CXCR4.

机构信息

Laboratory of Virus Control, Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan.

出版信息

Int J Biochem Cell Biol. 2010 Sep;42(9):1482-8. doi: 10.1016/j.biocel.2010.05.005. Epub 2010 May 16.

DOI:10.1016/j.biocel.2010.05.005

PMID:20580677

Abstract

Rev, a viral regulatory protein of HIV-1, binds through its arginine-rich domain to the Rev-responsive element (RRE), a secondary structure in transcribed HIV-1 RNA. Binding of Rev to RRE mediates export of singly spliced or unspliced mRNAs from the nucleus to the cytoplasm. It has been previously shown that a certain arginine-rich peptide exhibits not only RRE-binding ability but also cell permeability and antagonism of CXCR4, one of the major coreceptors of HIV-1. Here we designed and synthesized arginine-rich peptides derived from the RNA-binding domain of Rev (Rev(34-50)) and evaluated their anti-HIV-1 activities. Rev(34-50)-A(4)C, comprising Rev(34-50) with AAAAC at the C-terminus to increase the alpha-helicity, inhibited HIV-1 entry by CXCR4 antagonism and virus production in persistently HIV-1-infected PM1-CCR5 cells. Interestingly, similar motif of human lymphotropic virus type I Rex (Rex(1-21)) also exerted moderate anti-HIV-1 activity. These results indicate that arginine-rich peptide, Rev(34-50)-A(4)C exerts dual antagonism against CXCR4 and Rev.

摘要

Rev 是 HIV-1 的一种病毒调节蛋白，它通过富含精氨酸的结构域与 Rev 反应元件（RRE）结合，RRE 是转录的 HIV-1 RNA 中的二级结构。Rev 与 RRE 的结合介导了单剪接或未剪接的 mRNA 从细胞核输出到细胞质。先前已经表明，某些富含精氨酸的肽不仅具有 RRE 结合能力，而且还具有细胞通透性，并能拮抗 HIV-1 的主要核心受体之一 CXCR4。在这里，我们设计并合成了源自 Rev（Rev(34-50)）RNA 结合结构域的富含精氨酸的肽，并评估了它们的抗 HIV-1 活性。Rev(34-50)-A(4)C，由 C 末端的 AAAAC 组成，以增加α-螺旋性，通过拮抗 CXCR4 抑制 HIV-1 进入和持续感染 HIV-1 的 PM1-CCR5 细胞中的病毒产生。有趣的是，人类嗜淋巴细胞病毒 I Rex（Rex(1-21)）的类似基序也表现出适度的抗 HIV-1 活性。这些结果表明，富含精氨酸的肽 Rev(34-50)-A(4)C 对 CXCR4 和 Rev 具有双重拮抗作用。