Peptides P4 and P7 derived from E protein inhibit entry of dengue virus serotype 2 via interacting with β3 integrin
Peptides P4 and P7 derived from E protein inhibit entry of dengue virus serotype 2 via interacting with β3 integrin
复制标题
源自 E 蛋白的肽 P4 和 P7 通过与 β3 整合素相互作用抑制登革热病毒血清型 2 的进入
DOI：
10.1016/j.antiviral.2018.04.018
复制
发表时间：
2018-07-01
影响因子：
7.6
通讯作者：
An, Jing
中科院分区：
文献类型：
--
作者：
Cui, Xiaoyun;Wu, Yanhua;An, Jing
登革病毒(DENV)感染已成为全球严重的公共卫生问题。然而，目前还没有特定的抗病毒药物可用。在本研究中，我们发现DENV2感染可增强人脐静脉内皮细胞(HUVECs)β3整合素的表达，且DENV2抗原与β3整合素共定位。DENV2包膜蛋白(E)与β3整合素直接相互作用，相互作用部位位于E蛋白(EDIII)的第三结构域。根据EDIII的氨基酸序列设计了几个合成肽，P4和P7以剂量依赖的方式抑制DENV2进入血管内皮细胞。两种多肽对P4和P7的IC50分别为19.08+/-2.52和12.86+/-5.96 mU/M。此外，含有PG环的P7也能抑制DENV1进入血管内皮细胞，而不含P4。我们的结果提示了一种新的机制，即β3整合素和EDIII之间的相互作用参与了DENV的进入。这些多肽对病毒侵入的抑制作用的研究结果对抗DENV药物的设计具有重要意义。
Dengue virus (DENV) infection has become a severe public health problem worldwide. However, there is no specific antiviral drug available yet. In this study, we found that DENV serotype 2 (DENV2) infection enhanced the expression of beta 3 integrin on human umbilical vein endothelial cells (HUVECs) and that DENV2 antigens co localized with beta 3 integrin. DENV2 envelope protein (E) directly interacted with beta 3 integrin, and their interacting sites were located at domain III of E protein (EDIII). Several synthetic peptides were designed based on the amino acid sequence of EDIII, and peptides P4 and P7 could inhibit DENV2 entry into HUVECs in a dose-dependent manner. The inhibitory concentration (IC50) of the two peptides was 19.08 +/- 2.52 mu M for P4 and 12.86 +/- 5.96 mu M for P7. Moreover, P7 containing an PG-loop, but not P4, could also inhibit DENV1 entry into HUVECs. Our results suggest a novel mechanism in which interaction between beta 3 integrin and EDIII is involved in DENV entry. The findings on the inhibitory effect of the peptides on viral entry have significance for anti-DENV drug design.