Inhibition of phospholipid biosynthesis decreases the activity of the tombusvirus replicase and alters the subcellular localization of replication proteins

Monika Sharma, Zsuzsanna Sasvari, Peter D. Nagy

Research output: Contribution to journalArticlepeer-review

56 Scopus citations

Abstract

Replication of plus-strand RNA viruses depends on lipids present in cellular membranes. Recent genome-wide screens have revealed that eight phospholipid biosynthesis genes affected the replication of Tomato bushy stunt virus (TBSV) in yeast model host. To test the importance of phospholipids in TBSV replication, we studied one of the identified genes, namely INO2, which forms a heterodimer with Ino4, and is a transcription activator involved in regulation of phospholipid biosynthesis. Deletion of INO2, or double deletion of INO2/INO4, reduced TBSV replication and inhibited the activity of the viral replicase complex. In addition, the stability of the viral replication protein is decreased as well as the localization pattern of the viral protein changed dramatically in ino2Δino4Δ yeast. Over-expression of Opi1, a repressor of Ino2 and phospholipid biosynthesis, also inhibited TBSV RNA accumulation. In contrast, over-expression of Ino2 stimulated TBSV RNA accumulation. We also observed an inhibitory effect on Flock house virus (FHV) replication and the reduced stability of the FHV replication protein in ino2Δino4Δ yeast. These data are consistent with the important role of phospholipids in RNA virus replication.

Original languageEnglish
Pages (from-to)141-152
Number of pages12
JournalVirology
Volume415
Issue number2
DOIs
StatePublished - Jul 5 2011

Bibliographical note

Funding Information:
The authors thank Drs. Daniel Barajas, and Judit Pogany for valuable comments. pYES-His92 and pYES-His33 were prepared and provided by. T. Panavas. This work was supported by the National Science Foundation ( IOB-0517218 ), NIH-NIAID ( 5R21AI072170-02 ) and the K entucky Tobacco Research and Development Center to PDN.

Keywords

  • Cellular localization
  • Flock House virus
  • Host membrane
  • Host-virus interaction
  • Phospholipid
  • Replication
  • Tomato bushy stunt virus
  • Viral replicase

ASJC Scopus subject areas

  • Virology

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