Identification of NECTIN1 as a novel restriction factor for flavivirus infection

文献类型： 外文期刊

第一作者： Qi, Shuhui

作者： Qi, Shuhui;Sun, Chao;Wang, Jing;Wo, Lijing;Li, Yongfeng;Wang, Chaonan;Zhang, Ying;Bian, Haiqiao;Guo, Yongqi;Gao, Ming;Wang, Menghang;Tang, Yandong;Zhu, Yuanmao;Xue, Fei;Jiang, Zhigang;Yin, Xin;Qi, Shuhui;Pang, Quanhai;Wang, Jing

作者机构：

关键词： NECTIN1; BVDV; Flaviviridae family; CSFV; JEV; ZIKV; restriction factor

期刊名称：MBIO （ 影响因子：4.7； 五年影响因子：5.5 ）

ISSN：

年卷期： 2024 年 15 卷 12 期

页码：

收录情况： SCI

摘要： Nectin cell adhesion molecule 1 (NECTIN1) is a cell adhesion molecule that belongs to the immunoglobulin superfamily. It has been considered the most ubiquitous receptor for herpesviruses. However, in the context of flavivirus infection, its role was previously unknown. In this study, we described an arrayed siRNA screen mainly targeting Ig-like proteins that showed NECTIN1-restricted bovine viral diarrhea virus (BVDV) infection. We demonstrated that the depletion of NECTIN1 could significantly enhance the infection of both biotypes and multiple genotypes of BVDV, including BVDV-1a, -1b, -1c, -1p, -1m, -1v, and -2a. Notably, the IgV of NECTIN1 has emerged as the key domain restricting BVDV infection. Moreover, NECTIN1 inhibited BVDV attachment without exerting a significant influence on BVDV translation or transcription. Furthermore, we demonstrated that both NECTIN1 and CD46 could bind to BVDV E2, while the binding affinity of NECTIN1 for BVDV E2 was greater than that for CD46. We further identified that the BVDV E2 domain DD was a key domain of BVDV interacting with NECTIN1. In addition, we showed that NECTIN1 inhibited infections by classical swine fever virus (CSFV), Japanese encephalitis virus (JEV), and Zika virus (ZIKV), which belong to the Flaviviridae family, but had limited effects on bluetongue virus (BTV), vesicular stomatitis virus (VSV), Akabane virus (AKAV), and Sindbis virus (SINV). Overall, our study has important implications for understanding the entry of BVDV and revealed a novel role for NECTIN1 as a restriction factor that inhibits flavivirus infection.

分类号：

  • 相关文献
作者其他论文 更多>>

微信小程序