正义RNA病毒侵染宿主细胞后往往重塑细胞内膜系统形成病毒复制的场所。申请人前期研究工作证实甜菜黑色焦枯病毒(Beet black scorch virus，BBSV)可诱导内质网(ER)膜结构发生改变进而形成复制小泡，但是对于何种宿主因子参与BBSV诱导ER膜结构的弯曲在很大程度上未知，最近我们的研究结果表明，定位于ER的reticulon（RTN）家族蛋白是BBSV侵染所必需，基于此，本申请课题拟深入研究RTNs蛋白在BBSV复制中的作用机理，明确RTNs蛋白如何参与BBSV的复制，重点分析RTNs蛋白功能的异常对BBSV诱导ER膜弯曲和形成复制小泡的影响，尝试建立BBSV复制、RTNs蛋白、内质网胁迫和ER自噬之间的关联，最终建立RTNs蛋白参与BBSV侵染的机制模型，为深入理解BBSV复制过程中与宿主互作的分子和细胞机理提供新的科学证据，也为研究其他在ER膜上进行复制的病毒提供参考。

Positive-stranded RNA virus always remodels the endomembrane system to form the virus replication factories. Our previous work indicated that Beet black scorch virus (BBSV), a member in the genus Betanecrovirus of family Tombusviridae, induces the membrane curvature of the endoplasmic reticulum (ER) to form the viral replication vesicles. However, the host factors that involved in the rearrangement of ER during BBSV infection remains largely unknown. Recently, our preliminary data suggested that the ER-localized reticulon family proteins (RTNs) are required for BBSV infection. Based upon this, the proposal here aims to investigate the functional roles of RTNs in BBSV replication and determine how the RTNs participate in the BBSV replication. The effect of functional disruption of RTNs on the ER membrane remodeling and the build-up of membranous replication vesicles will be particularly studied. This project also aims to establish the functional link between BBSV replication, RTNs, ER stress and ER-phagy, thus presenting a mechanistic model of the functional roles of RTNs in BBSV replication at last. Our studies would provide new evidence for further understanding the molecular mechanisms underlying the BBSV-host interaction, and also provide a reference for studying other viruses that replicate on ER-derived membranes.