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.