title: Tombusviruses upregulate phospholipid biosynthesis via interaction between p33 replication protein and yeast lipid sensor proteins during virus replication in yeast.
abstract: Positive-stranded RNA viruses induce new membranous structures and promote membrane proliferation in infected cells to facilitate viral replication. In this paper, the authors show that a plant-infecting tombusvirus upregulates transcription of phospholipid biosynthesis genes, such as INO1, OPI3 and CHO1, and increases phospholipid levels in yeast model host. This is accomplished by the viral p33 replication protein, which interacts with Opi1p FFAT domain protein and Scs2p VAP protein. Opi1p and Scs2p are phospholipid sensor proteins and they repress the expression of phospholipid genes. Accordingly, deletion of OPI1 transcription repressor in yeast has a stimulatory effect on TBSV RNA accumulation and enhanced tombusvirus replicase activity in an in vitro assay. Altogether, the presented data convincingly demonstrate that de novo lipid biosynthesis is required for optimal TBSV replication. Overall, this work reveals that a (+)RNA virus reprograms the phospholipid biosynthesis pathway in a unique way to facilitate its replication in yeast cells.
authors.affiliation: Department of Plant Pathology, University of Kentucky, Lexington, KY 40546, United States.
authors.forename: Daniel
authors.initials: D
authors.lastname: Barajas
authors.affiliation: Department of Plant Pathology, University of Kentucky, Lexington, KY 40546, United States.
authors.forename: Kai
authors.initials: K
authors.lastname: Xu
authors.affiliation: Department of Plant Pathology, University of Kentucky, Lexington, KY 40546, United States.
authors.forename: Monika
authors.initials: M
authors.lastname: Sharma
authors.affiliation: Department of Plant Pathology, University of Kentucky, Lexington, KY 40546, United States.
authors.forename: Cheng-Yu
authors.initials: CY
authors.lastname: Wu
authors.affiliation: Department of Plant Pathology, University of Kentucky, Lexington, KY 40546, United States. Electronic address: pdnagy2@uky.edu.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Nagy
mesh_terms: D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal / Q000502:physiology; D015967:Gene Expression Regulation, Viral / Q000502:physiology; D010743:Phospholipids / Q000096:biosynthesis*; D010957:Plasmids / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000378:metabolism / Q000821:virology*; D017864:Tombusvirus / Q000502:physiology*; D015854:Up-Regulation; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication / Q000502:physiology*
chemical_list: D005656:Fungal Proteins; D010743:Phospholipids; D014764:Viral Proteins
keywords: FFAT domain; Membrane proliferation; Phosphatidic acid; Phospholipids; Replicase; Replication in vitro; Tomato bushy stunt virus; Transcription repressor; VAP domain; Yeast host