PDF(Pubmed)
Abstract：
Nipah virus (NiV) is a highly lethal zoonotic virus with a potential large-scale outbreak, which poses a great threat to world health and security. In order to explore more potential factors associated with NiV, a proximity labeling method was applied to investigate the F, G, and host protein interactions systematically. We screened 1996 and 1524 high-confidence host proteins that interacted with the NiV fusion (F) glycoprotein and attachment (G) glycoprotein in HEK293T cells by proximity labeling technology, and 863 of them interacted with both F and G. The results of GO and KEGG enrichment analysis showed that most of these host proteins were involved in cellular processes, molecular binding, endocytosis, tight junction, and other functions. Cytoscape software (v3.9.1) was used for visual analysis, and the results showed that Cortactin (CTTN), Serpine mRNA binding protein 1 (SERBP1), and stathmin 1 (STMN1) were the top 20 proteins and interacted with F and G, and were selected for further validation. We observed colocalization of F-CTTN, F-SERBP1, F-STMN1, G-CTTN, G-SERBP1, and G-STMN1 using confocal fluorescence microscopy, and the results showed that CTTN, SERBP1, and STMN1 overlapped with NiV F and NiV G in HEK293T cells. Further studies found that CTTN can significantly inhibit the infection of the Nipah pseudovirus (NiVpv) into host cells, while SERBP1 and STMN1 had no significant effect on pseudovirus infection. In addition, CTTN can also inhibit the infection of the Hendra pseudovirus (HeVpv) in 293T cells. In summary, this study revealed that the potential host proteins interacted with NiV F and G and demonstrated that CTTN could inhibit NiVpv and HeVpv infection, providing new evidence and targets for the study of drugs against these diseases.
摘要：
尼帕病毒(NiV)是一种高致死性人畜共患病毒,有可能大规模爆发。这对世界健康和安全构成了巨大威胁。为了探索更多与NiV相关的潜在因素，一种邻近标记方法被用来研究F，G,和宿主蛋白质相互作用系统。我们通过邻近标记技术筛选了1996年和1524年与HEK293T细胞中的NiV融合（F）糖蛋白和附着（G）糖蛋白相互作用的高置信度宿主蛋白，和863与F和G相互作用。GO和KEGG富集分析的结果表明，这些宿主蛋白中的大多数参与细胞过程，分子结合，内吞作用,紧密连接,和其他功能。使用Cytoscape软件（v3.9.1）进行可视化分析，结果表明，Cortactin(CTTN)，SerpinemRNA结合蛋白1（SERBP1），和stathmin1（STMN1）是前20个蛋白质，并与F和G相互作用，并选择进行进一步验证。我们观察到F-CTTN的共定位，F-SERBP1,F-STMN1,G-CTTN,G-SERBP1和G-STMN1使用共聚焦荧光显微镜，结果显示CTTN,HEK293T细胞中SERBP1和STMN1与NiVF和NiVG重叠。进一步研究发现,CTTN能显著抑制尼帕假病毒(NiVpv)对宿主细胞的感染,而SERBP1和STMN1对假病毒感染无明显影响。此外,CTTN还可以抑制Hendra假病毒(HeVpv)在293T细胞中的感染。总之,这项研究揭示了潜在的宿主蛋白与NiVF和G相互作用，并证明CTTN可以抑制NiVpv和HeVpv感染，为针对这些疾病的药物研究提供新的证据和靶点。
