Department of Plant Pathology, University of Kentucky, Plant Science Building, Lexington, KY 40546, United States.
Department of Plant Pathology, University of Kentucky, Plant Science Building, Lexington, KY 40546, United States.
Virology. 2018 Jun;519:207-222. doi: 10.1016/j.virol.2018.04.010. Epub 2018 May 7.
Similar to other (+)RNA viruses, tomato bushy stunt virus (TBSV) utilizes metabolites, lipids, membranes, and co-opted host factors during replication. The coordination of cell metabolism and growth with environmental cues is performed by the target of rapamycin (TOR) kinase in eukaryotic cells. In this paper, we find that TBSV replication partially inhibits TOR activity, likely due to recruitment of glycolytic enzymes to the viral replication compartment, which results in reduced ATP levels in the cytosol. Complete inhibition of TOR activity with rapamycin in yeast or AZD8055 inhibitor in plants reduces tombusvirus replication. We find that high glucose concentration, which stimulates TOR activity, enhanced tombusvirus replication in yeast. Depletion of yeast Sch9 or plant S6K1 kinase, a downstream effector of TOR, also inhibited tombusvirus replication in yeast and plant or the assembly of the viral replicase in vitro. Altogether, the TOR pathway is crucial for TBSV to replicate efficiently in hosts.
类似于其他（+）RNA 病毒，番茄丛矮病毒（TBSV）在复制过程中利用代谢物、脂质、膜和被劫持的宿主因子。真核细胞中，雷帕霉素靶蛋白（TOR）激酶协调细胞代谢和生长与环境信号。在本文中，我们发现 TBSV 复制部分抑制 TOR 活性，可能是由于糖酵解酶被招募到病毒复制区，导致细胞质中 ATP 水平降低。用雷帕霉素在酵母中或用 AZD8055 抑制剂在植物中完全抑制 TOR 活性会降低番茄丛矮病毒的复制。我们发现，高葡萄糖浓度会刺激 TOR 活性，从而增强酵母中的番茄丛矮病毒复制。耗尽酵母 Sch9 或植物 S6K1 激酶（TOR 的下游效应物）也会抑制酵母和植物中的番茄丛矮病毒复制或体外病毒复制酶的组装。总的来说，TOR 途径对 TBSV 在宿主中高效复制至关重要。
