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

Jun ichi Inaba; Peter D. Nagy

doi:10.1016/j.virol.2018.04.010

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

Jun ichi Inaba, Peter D. Nagy

Plant Pathology

Research output: Contribution to journal › Article › peer-review

17 Scopus citations

Abstract

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 language	English
Pages (from-to)	207-222
Number of pages	16
Journal	Virology
Volume	519
DOIs	https://doi.org/10.1016/j.virol.2018.04.010
State	Published - 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.

Keywords

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

ASJC Scopus subject areas

Virology

Access to Document

10.1016/j.virol.2018.04.010

Cite this

@article{299d15df948c4be181cb6655b1179c99,

title = "Tombusvirus RNA replication depends on the TOR pathway in yeast and plants",

abstract = "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.",

keywords = "Glycolysis, In vitro, Plant, Replication, Ribonucleotide synthesis, TBSV, TOR kinase, Tomato bushy stunt virus, Virus-host interaction, Yeast",

author = "Inaba, {Jun ichi} and Nagy, {Peter D.}",

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: {\textcopyright} 2018 Elsevier Inc.",

year = "2018",

month = jun,

doi = "10.1016/j.virol.2018.04.010",

language = "English",

volume = "519",

pages = "207--222",

}

TY - JOUR

T1 - Tombusvirus RNA replication depends on the TOR pathway in yeast and plants

AU - Inaba, Jun ichi

AU - Nagy, Peter D.

N1 - 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.

PY - 2018/6

Y1 - 2018/6

N2 - 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.

AB - 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.

KW - Glycolysis

KW - In vitro

KW - Plant

KW - Replication

KW - Ribonucleotide synthesis

KW - TBSV

KW - TOR kinase

KW - Tomato bushy stunt virus

KW - Virus-host interaction

KW - Yeast

UR - http://www.scopus.com/inward/record.url?scp=85046721253&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85046721253&partnerID=8YFLogxK

U2 - 10.1016/j.virol.2018.04.010

DO - 10.1016/j.virol.2018.04.010

M3 - Article

C2 - 29734044

AN - SCOPUS:85046721253

SN - 0042-6822

VL - 519

SP - 207

EP - 222

JO - Virology

JF - Virology

ER -

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this