Tombusvirus RNA replication depends on the TOR pathway in yeast and plants

Jun ichi Inaba, Peter D. Nagy

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


Similar to other (+)RNA viruses, tomato bushy stunt virus (TBSV) utilizes metabolites, lipids, membranes, and co-opted host factors during replication. The coordination of cell metabolism and growth with environmental cues is performed by the target of rapamycin (TOR) kinase in eukaryotic cells. In this paper, we find that TBSV replication partially inhibits TOR activity, likely due to recruitment of glycolytic enzymes to the viral replication compartment, which results in reduced ATP levels in the cytosol. Complete inhibition of TOR activity with rapamycin in yeast or AZD8055 inhibitor in plants reduces tombusvirus replication. We find that high glucose concentration, which stimulates TOR activity, enhanced tombusvirus replication in yeast. Depletion of yeast Sch9 or plant S6K1 kinase, a downstream effector of TOR, also inhibited tombusvirus replication in yeast and plant or the assembly of the viral replicase in vitro. Altogether, the TOR pathway is crucial for TBSV to replicate efficiently in hosts.

Original languageEnglish
Pages (from-to)207-222
Number of pages16
StatePublished - Jun 2018

Bibliographical note

Funding Information:
We thank Dr. Judit Pogany for comments on the manuscript. The AtS6K1 plasmid was a generous gift from Dr. Jen Sheen (Harvard). The yeast strain DBY746 and the deletion yeast strains, rhr2Δ, sch9Δ, rhr2Δ/sch9Δ were obtained from Dr. Valter D. Longo (University of Southern California). The yeast strain W303-1B was a generous gift from Dr. Zhigang Wang (University of Kentucky). The authors thank Drs. H. Imamura and H. Noji for providing plasmids pRSET-ATeam YEMK and pRSET-ATeam RK . This work was supported by NSF-MCB ( 1517751 ).

Publisher Copyright:
© 2018 Elsevier Inc.


  • Glycolysis
  • In vitro
  • Plant
  • Replication
  • Ribonucleotide synthesis
  • TBSV
  • TOR kinase
  • Tomato bushy stunt virus
  • Virus-host interaction
  • Yeast

ASJC Scopus subject areas

  • Virology


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