CXCR4-derived synthetic peptides inducing anti-HIV-1 antibodies
CXCR4-derived synthetic peptides inducing anti-HIV-1 antibodies
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DOI：
10.1016/j.bmc.2013.09.037
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发表时间：
2013-11-15
影响因子：
3.5
通讯作者：
Tamamura, Hirokazu
中科院分区：
文献类型：
--
作者：
Hashimoto, Chie;Nomura, Wataru;Tamamura, Hirokazu
尽管人类免疫缺陷病毒I型（HIV-1）已被发现近30年，但HIV-1的高易变性阻碍了有效艾滋病疫苗的开发。HIV-1共受体CCR5和CXCR4在遗传上是稳定的，但病毒蛋白可能在感染过程中迅速突变。CXCR4是一个七跨膜G蛋白偶联受体，具有一个n端区（NT）和三个细胞外环（ECL1-3）。先前的研究表明，cxcr4 - ed衍生的肽通过与HIV-1包膜糖蛋白gp120相互作用来抑制HIV-1的进入。在本研究中，研究了cxcr4衍生肽的抗原性，并评估了诱导抗血清的抗hiv -1效果。发现cxcr4 - ed衍生抗原分子对小鼠具有免疫作用，表明线性肽比环状肽具有更高的抗原性。L1和l2诱导的抗血清明显抑制HIV-1的进入，而抗n1抗体没有抑制活性。这项研究为设计针对人类蛋白质的艾滋病疫苗提供了有希望的例子，这些疫苗可以克服HIV-1的易变性。(C) 2013 Elsevier Ltd.版权所有。
Despite almost 30 years since the identification of the human immunodeficiency virus type I (HIV-1), development of effective AIDS vaccines has been hindered by the high mutability of HIV-1. The HIV-1 co-receptors CCR5 and CXCR4 are genetically stable, but viral proteins may mutate rapidly during the course of infection. CXCR4 is a seven transmembrane G protein-coupled receptor, possessing an N-terminal region (NT) and three extracellular loops (ECL1-3). Previous studies have shown that the CXCR4-ED-derived peptides inhibit the entry of HIV-1 by interacting with gp120, an HIV-1 envelope glycoprotein. In the present study, antigenicity of CXCR4-derived peptides has been investigated and the anti-HIV-1 effects of induced antisera have been assessed. It was found that CXCR4-ED-derived antigen molecules immunize mice, showing that the linear peptides have higher antigenicity than the cyclic peptides. The L1- and L2-induced antisera inhibited the HIV-1 entry significantly, while anti-N1 antibodies have no inhibitory activity. This study produced promising examples for the design of AIDS vaccines which target the human protein and can overcome mutability of HIV-1. (C) 2013 Elsevier Ltd. All rights reserved.