Co-opted Oxysterol-Binding ORP and VAP Proteins Channel Sterols to RNA Virus Replication Sites via Membrane Contact Sites

被引:96
作者
Barajas, Daniel [1 ]
Xu, Kai [1 ]
de Castro Martin, Isabel Fernandez [2 ]
Sasvari, Zsuzsanna [1 ]
Brandizzi, Federica [3 ]
Risco, Cristina [2 ]
Nagy, Peter D. [1 ]
机构
[1] Univ Kentucky, Dept Plant Pathol, Lexington, KY 40546 USA
[2] Ctr Nacl Biotecnol CNB CSIC, Cell Struct Lab, Madrid, Spain
[3] Michigan State Univ, MSU DOE Plant Res Lab, E Lansing, MI 48824 USA
基金
美国国家科学基金会;
关键词
BUSHY-STUNT-VIRUS; GENES AFFECTING REPLICATION; HOST FACTORS; HEPATITIS-C; ENDOPLASMIC-RETICULUM; TOMBUSVIRUS REPLICATION; LIPID-METABOLISM; VIRAL-RNA; MODEL HOST; SCREEN REVEALS;
D O I
10.1371/journal.ppat.1004388
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Viruses recruit cellular membranes and subvert cellular proteins involved in lipid biosynthesis to build viral replicase complexes and replication organelles. Among the lipids, sterols are important components of membranes, affecting the shape and curvature of membranes. In this paper, the tombusvirus replication protein is shown to co-opt cellular Oxysterol-binding protein related proteins (ORPs), whose deletion in yeast model host leads to decreased tombusvirus replication. In addition, tombusviruses also subvert Scs2p VAP protein to facilitate the formation of membrane contact sites (MCSs), where membranes are juxtaposed, likely channeling lipids to the replication sites. In all, these events result in redistribution and enrichment of sterols at the sites of viral replication in yeast and plant cells. Using in vitro viral replication assay with artificial vesicles, we show stimulation of tombusvirus replication by sterols. Thus, co-opting cellular ORP and VAP proteins to form MCSs serves the virus need to generate abundant sterol-rich membrane surfaces for tombusvirus replication.
引用
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页数:18
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