title: Co-opted oxysterol-binding ORP and VAP proteins channel sterols to RNA virus replication sites via membrane contact sites.
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.
authors.affiliation: Department of Plant Pathology, University of Kentucky, Lexington, Kentucky, United States of America.
authors.forename: Daniel
authors.initials: D
authors.lastname: Barajas
authors.affiliation: Department of Plant Pathology, University of Kentucky, Lexington, Kentucky, United States of America.
authors.forename: Kai
authors.initials: K
authors.lastname: Xu
authors.affiliation: Cell Structure Laboratory, Centro Nacional de Biotecnología (CNB-CSIC), Campus de Cantoblanco, Madrid, Spain.
authors.forename: Isabel Fernández
authors.initials: IF
authors.lastname: de Castro Martín
authors.affiliation: Department of Plant Pathology, University of Kentucky, Lexington, Kentucky, United States of America.
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Sasvari
authors.affiliation: MSU-DOE Plant Research Laboratory, Michigan State University, East Lansing, Michigan, United States of America.
authors.forename: Federica
authors.initials: F
authors.lastname: Brandizzi
authors.affiliation: Cell Structure Laboratory, Centro Nacional de Biotecnología (CNB-CSIC), Campus de Cantoblanco, Madrid, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Risco
authors.affiliation: Department of Plant Pathology, University of Kentucky, Lexington, Kentucky, United States of America.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Nagy
mesh_terms: D004261:DNA Replication / Q000235:genetics; D051336:Mitochondrial Membranes / Q000378:metabolism / Q000821:virology*; D012441:Saccharomyces cerevisiae; D013261:Sterols / Q000378:metabolism*; D017864:Tombusvirus / Q000502:physiology*; D014764:Viral Proteins / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D013261:Sterols; D014764:Viral Proteins