Inflammatory Response and Infection Susceptibility Centre (iRiSC), School of Medical Science, Örebro University, 703 62 Örebro, Sweden.
Viruses. 2021 Jun 22;13(7):1198. doi: 10.3390/v13071198.
The endoplasmic reticulum (ER) of eukaryotic cells is a dynamic organelle, which undergoes continuous remodeling. At the three-way tubular junctions of the ER, the lunapark (LNP) protein acts as a membrane remodeling factor to stabilize these highly curved membrane junctions. In addition, during flavivirus infection, the ER membrane is invaginated to form vesicles (Ve) for virus replication. Thus, LNP may have roles in the generation or maintenance of the Ve during flavivirus infection. In this study, our aim was to characterize the functions of LNP during flavivirus infection and investigate the underlying mechanisms of these functions. To specifically study virus replication, we generated cell lines expressing replicons of West Nile virus (Kunjin strain) or Langat virus. By using these replicon platforms and electron microscopy, we showed that depletion of LNP resulted in reduced virus replication, which is due to its role in the generation of the Ve. By using biochemical assays and high-resolution microscopy, we found that LNP is recruited to the Ve and the protein interacts with the nonstructural protein (NS) 4B. Therefore, these data shed new light on the interactions between flavivirus and host factors during viral replication.
真核细胞的内质网（ER）是一个动态的细胞器，它会不断进行重塑。在内质网的三通管状连接处，LNP 蛋白作为一种膜重塑因子，稳定这些高度弯曲的膜连接处。此外，在黄病毒感染期间，内质网膜向内凹陷形成囊泡（Ve）以进行病毒复制。因此，LNP 可能在黄病毒感染期间参与 Ve 的产生或维持。在这项研究中，我们的目的是研究 LNP 在黄病毒感染过程中的作用，并探讨这些功能的潜在机制。为了专门研究病毒复制，我们生成了表达西尼罗河病毒（Kunjin 株）或 Langat 病毒复制子的细胞系。通过使用这些复制子平台和电子显微镜，我们发现 LNP 的耗竭会导致病毒复制减少，这是由于它在 Ve 的产生中的作用。通过生化测定和高分辨率显微镜，我们发现 LNP 被招募到 Ve 上，并且该蛋白与非结构蛋白（NS）4B 相互作用。因此，这些数据为病毒复制期间黄病毒与宿主因子之间的相互作用提供了新的视角。
