Perilipin-2 is critical for efficient lipoprotein and hepatitis C virus particle production
Perilipin-2 is critical for efficient lipoprotein and hepatitis C virus particle production
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DOI：
10.1242/jcs.217042
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发表时间：
2019-01-01
影响因子：
4
通讯作者：
Herker, Eva
中科院分区：
文献类型：
--
作者：
Lassen, Susan;Gruettner, Cordula;Herker, Eva
在肝细胞中，PLIN 2是包被脂滴（LD）的主要蛋白质，脂滴是丙型肝炎病毒（HCV）劫持用于病毒体形态发生的细胞器。我们研究了PLIN 2缺陷对LD和HCV感染的后果。PLIN 2的敲低不影响LD稳态，可能是由于PLIN 3的补偿，但严重损害了HCV颗粒的产生。PLIN 2敲除细胞具有稍大的LD，蛋白质组成改变，局部脂肪酶活性增强和β-氧化能力更高。电子显微照片显示，PLIN 2敲低后，LD和HCV诱导的囊泡结构被ER衍生的双膜囊紧密包围。引人注目的是，HCV核心和NS 5A蛋白的LD进入在PLIN 2缺陷细胞中受到限制，这与细胞内感染性较低且密度较高的HCV颗粒形成减少相关，表明成熟缺陷。PLIN 2耗竭还由于溶酶体降解而降低蛋白水平和ApoE分泌，但不影响含ApoE脂蛋白的密度。然而，PLIN 2缺陷细胞中ApoE过表达不能恢复HCV传播。因此，PLIN 2的表达是必需的核心和NS 5A蛋白运输到LDs，并形成功能性低密度HCV颗粒前ApoE incorporation.This文章有一个相关的第一人称采访的论文的第一作者。
In hepatocytes, PLIN2 is the major protein coating lipid droplets (LDs), an organelle the hepatitis C virus (HCV) hijacks for virion morphogenesis. We investigated the consequences of PLIN2 deficiency on LDs and on HCV infection. Knockdown of PLIN2 did not affect LD homeostasis, likely due to compensation by PLIN3, but severely impaired HCV particle production. PLIN2-knockdown cells had slightly larger LDs with altered protein composition, enhanced local lipase activity and higher beta-oxidation capacity. Electron micrographs showed that, after PLIN2 knockdown, LDs and HCVinduced vesicular structures were tightly surrounded by ER-derived double-membrane sacs. Strikingly, the LD access for HCV core and NS5A proteins was restricted in PLIN2-deficient cells, which correlated with reduced formation of intracellular HCV particles that were less infectious and of higher density, indicating defects in maturation. PLIN2 depletion also reduced protein levels and secretion of ApoE due to lysosomal degradation, but did not affect the density of ApoE-containing lipoproteins. However, ApoE overexpression in PLIN2-deficient cells did not restore HCV spreading. Thus, PLIN2 expression is required for trafficking of core and NS5A proteins to LDs, and for formation of functional low-density HCV particles prior to ApoE incorporation.This article has an associated First Person interview with the first author of the paper.