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

Overview

Journal PLoS Pathog

Specialty Microbiology

Date 2014 Oct 21

PMID 25329172

Citations 60

Authors

Daniel Barajas

Kai Xu

Isabel Fernandez de Castro Martin

Zsuzsanna Sasvari

Federica Brandizzi

Cristina Risco

Peter D Nagy

Affiliations

Soon will be listed here.

Abstract

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.

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