State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730000, China; Gansu Province Research Center for Basic Disciplines of Pathogen Biology, Lanzhou 730046, China.
State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730000, China; Gansu Province Research Center for Basic Disciplines of Pathogen Biology, Lanzhou 730046, China.
Virol Sin. 2024 Jun;39(3):378-389. doi: 10.1016/j.virs.2024.03.005. Epub 2024 Mar 16.
Foot-and-mouth disease (FMD) is a highly contagious and economically important disease, which is caused by the FMD virus (FMDV). Although the cell receptor for FMDV has been identified, the specific mechanism of FMDV internalization after infection remains unknown. In this study, we found that kinesin family member 5B (KIF5B) plays a vital role during FMDV internalization. Moreover, we confirmed the interaction between KIF5B and FMDV structural protein VP1 by co-immunoprecipitation (Co-IP) and co-localization in FMDV-infected cells. In particular, the stalk [amino acids (aa) 413-678] domain of KIF5B was indispensable for KIF5B-VP1 interaction. Moreover, overexpression of KIF5B dramatically enhanced FMDV replication; consistently, knockdown or knockout of KIF5B suppressed FMDV replication. Furthermore, we also demonstrated that KIF5B promotes the internalization of FMDV via regulating clathrin uncoating. KIF5B also promotes the transmission of viral particles to early and late endosomes during the early stages of infection. In conclusion, our results demonstrate that KIF5B promotes the internalization of FMDV via regulating clathrin uncoating and intracellular transport. This study may provide a new therapeutic target for developing FMDV antiviral drugs.
口蹄疫(FMD)是一种高度传染性和具有重要经济意义的疾病,由口蹄疫病毒(FMDV)引起。尽管已经确定了 FMDV 的细胞受体,但感染后 FMDV 内化的具体机制仍不清楚。在本研究中,我们发现驱动蛋白家族成员 5B(KIF5B)在 FMDV 内化过程中起着至关重要的作用。此外,我们通过共免疫沉淀(Co-IP)和 FMDV 感染细胞中的共定位证实了 KIF5B 和 FMDV 结构蛋白 VP1 之间的相互作用。特别是 KIF5B 的茎(氨基酸(aa)413-678)结构域对于 KIF5B-VP1 相互作用是不可或缺的。此外,过表达 KIF5B 可显著增强 FMDV 的复制;相反,敲低或敲除 KIF5B 则抑制 FMDV 复制。此外,我们还证明 KIF5B 通过调节网格蛋白脱衣促进 FMDV 的内化。KIF5B 还在感染早期促进病毒颗粒向早期和晚期内体的转运。总之,我们的研究结果表明,KIF5B 通过调节网格蛋白脱衣和细胞内运输促进 FMDV 的内化。这项研究可能为开发 FMDV 抗病毒药物提供新的治疗靶点。