Institute of Molecular Life Sciences, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland; Life Science Zurich Graduate School, Molecular Life Sciences Program, Zurich, Switzerland.
Institute of Molecular Life Sciences, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
Cell Host Microbe. 2014 Nov 12;16(5):677-90. doi: 10.1016/j.chom.2014.10.003.
Similar to other positive-strand RNA viruses, rhinovirus, the causative agent of the common cold, replicates on a web of cytoplasmic membranes, orchestrated by host proteins and lipids. The host pathways that facilitate the formation and function of the replication membranes and complexes are poorly understood. We show that rhinovirus replication depends on host factors driving phosphatidylinositol 4-phosphate (PI4P)-cholesterol counter-currents at viral replication membranes. Depending on the virus type, replication required phosphatidylinositol 4-kinase class 3beta (PI4K3b), cholesteryl-esterase hormone-sensitive lipase (HSL) or oxysterol-binding protein (OSBP)-like 1, 2, 5, 9, or 11 associated with lipid droplets, endosomes, or Golgi. Replication invariably required OSBP1, which shuttles cholesterol and PI4P between ER and Golgi at membrane contact sites. Infection also required ER-associated PI4P phosphatase Sac1 and phosphatidylinositol (PI) transfer protein beta (PITPb) shunting PI between ER-Golgi. These data support a PI4P-cholesterol counter-flux model for rhinovirus replication.
类似于其他正链 RNA 病毒，鼻病毒（引起普通感冒的病原体）在细胞质膜网络上复制，由宿主蛋白和脂质协调。促进复制膜和复合物形成和功能的宿主途径知之甚少。我们表明，鼻病毒复制依赖于宿主因子，这些因子驱动病毒复制膜处的磷脂酰肌醇 4-磷酸（PI4P）-胆固醇反向流动。根据病毒类型，复制需要磷脂酰肌醇 4-激酶 3β（PI4K3b）、胆固醇酯酶激素敏感脂肪酶（HSL）或与脂滴、内体或高尔基体相关的氧化固醇结合蛋白（OSBP）样蛋白 1、2、5、9 或 11。复制始终需要 OSBP1，它在膜接触位点处将胆固醇和 PI4P 在 ER 和高尔基体之间穿梭。感染还需要内质网相关的 PI4P 磷酸酶 Sac1 和将 PI 在 ER-高尔基体之间穿梭的磷脂酰肌醇（PI）转移蛋白 beta（PITPb）。这些数据支持鼻病毒复制的 PI4P-胆固醇反向通量模型。
