Tomato bushy stunt virus Co-Opts the RNA-Binding Function of a Host Metabolic Enzyme for Viral Genomic RNA Synthesis

Robert Yung Liang Wang; Peter D. Nagy

doi:10.1016/j.chom.2008.02.005

Tomato bushy stunt virus Co-Opts the RNA-Binding Function of a Host Metabolic Enzyme for Viral Genomic RNA Synthesis

Robert Yung Liang Wang, Peter D. Nagy

Plant Pathology

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

141 Scopus citations

Abstract

Tomato bushy stunt virus (TBSV), a plus-stranded [(+)] RNA plant virus, incorporates the host metabolic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) into the viral replicase complex. Here, we show that, during TBSV replication in yeast, the yeast GAPDH Tdh2p moves from the cytosol to the peroxisomal membrane surface, the site of viral RNA synthesis. In yeast cells lacking Tdh2p, decreasing the levels of its functionally redundant homolog Tdh3p inhibited TBSV replication and resulted in equivalent levels of (+) and minus-stranded [(-)] viral RNA, in contrast to the hallmark excess of (+)RNA. Tdh2p specifically bound an AU pentamer sequence in the (-)RNA, suggesting that GAPDH promotes asymmetric RNA synthesis by selectively retaining the (-)RNA template in the replicase complex. Downregulation of GAPDH in a natural plant host decreased TBSV genomic RNA accumulation. Thus, TBSV co-opts the RNA-binding function of a metabolic protein, helping convert the host cell into a viral factory.

Original language	English
Pages (from-to)	178-187
Number of pages	10
Journal	Cell Host and Microbe
Volume	3
Issue number	3
DOIs	https://doi.org/10.1016/j.chom.2008.02.005
State	Published - Mar 13 2008

Bibliographical note

Funding Information:
We thank Dr. Saulius Serva for his preliminary experiments on the viral RNA binding by Tdh2p. We thank Dr. Dinesh-Kumar for pTRV1 and pTRV2 VIGS vectors; Dr. D. Lewandowski for the infectious TMV clone; and Drs. Mark Farman, Judit Pogany, David Smith, and Zsuzsanna Sasvari for critical reading of the manuscript and for very helpful suggestions. This work was supported by NIH-NIAID and by the Kentucky Tobacco Research and Development Center at the University of Kentucky, awarded to P.D.N.

Funding

We thank Dr. Saulius Serva for his preliminary experiments on the viral RNA binding by Tdh2p. We thank Dr. Dinesh-Kumar for pTRV1 and pTRV2 VIGS vectors; Dr. D. Lewandowski for the infectious TMV clone; and Drs. Mark Farman, Judit Pogany, David Smith, and Zsuzsanna Sasvari for critical reading of the manuscript and for very helpful suggestions. This work was supported by NIH-NIAID and by the Kentucky Tobacco Research and Development Center at the University of Kentucky, awarded to P.D.N.

Funders	Funder number
NIH-NIAID
National Institute of Allergy and Infectious Diseases	R21AI072170
The Kentucky Tobacco Research and Development Center
University of Kentucky

Keywords

CELLBIO
MICROBIO

ASJC Scopus subject areas

Parasitology
Microbiology
Virology

Access to Document

10.1016/j.chom.2008.02.005

Cite this

@article{3ecd13d7179c4c11ba5693fc56eb431f,

title = "Tomato bushy stunt virus Co-Opts the RNA-Binding Function of a Host Metabolic Enzyme for Viral Genomic RNA Synthesis",

abstract = "Tomato bushy stunt virus (TBSV), a plus-stranded [(+)] RNA plant virus, incorporates the host metabolic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) into the viral replicase complex. Here, we show that, during TBSV replication in yeast, the yeast GAPDH Tdh2p moves from the cytosol to the peroxisomal membrane surface, the site of viral RNA synthesis. In yeast cells lacking Tdh2p, decreasing the levels of its functionally redundant homolog Tdh3p inhibited TBSV replication and resulted in equivalent levels of (+) and minus-stranded [(-)] viral RNA, in contrast to the hallmark excess of (+)RNA. Tdh2p specifically bound an AU pentamer sequence in the (-)RNA, suggesting that GAPDH promotes asymmetric RNA synthesis by selectively retaining the (-)RNA template in the replicase complex. Downregulation of GAPDH in a natural plant host decreased TBSV genomic RNA accumulation. Thus, TBSV co-opts the RNA-binding function of a metabolic protein, helping convert the host cell into a viral factory.",

keywords = "CELLBIO, MICROBIO",

author = "Wang, {Robert Yung Liang} and Nagy, {Peter D.}",

note = "Funding Information: We thank Dr. Saulius Serva for his preliminary experiments on the viral RNA binding by Tdh2p. We thank Dr. Dinesh-Kumar for pTRV1 and pTRV2 VIGS vectors; Dr. D. Lewandowski for the infectious TMV clone; and Drs. Mark Farman, Judit Pogany, David Smith, and Zsuzsanna Sasvari for critical reading of the manuscript and for very helpful suggestions. This work was supported by NIH-NIAID and by the Kentucky Tobacco Research and Development Center at the University of Kentucky, awarded to P.D.N. ",

year = "2008",

month = mar,

day = "13",

doi = "10.1016/j.chom.2008.02.005",

language = "English",

volume = "3",

pages = "178--187",

number = "3",

}

TY - JOUR

T1 - Tomato bushy stunt virus Co-Opts the RNA-Binding Function of a Host Metabolic Enzyme for Viral Genomic RNA Synthesis

AU - Wang, Robert Yung Liang

AU - Nagy, Peter D.

N1 - Funding Information: We thank Dr. Saulius Serva for his preliminary experiments on the viral RNA binding by Tdh2p. We thank Dr. Dinesh-Kumar for pTRV1 and pTRV2 VIGS vectors; Dr. D. Lewandowski for the infectious TMV clone; and Drs. Mark Farman, Judit Pogany, David Smith, and Zsuzsanna Sasvari for critical reading of the manuscript and for very helpful suggestions. This work was supported by NIH-NIAID and by the Kentucky Tobacco Research and Development Center at the University of Kentucky, awarded to P.D.N.

PY - 2008/3/13

Y1 - 2008/3/13

N2 - Tomato bushy stunt virus (TBSV), a plus-stranded [(+)] RNA plant virus, incorporates the host metabolic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) into the viral replicase complex. Here, we show that, during TBSV replication in yeast, the yeast GAPDH Tdh2p moves from the cytosol to the peroxisomal membrane surface, the site of viral RNA synthesis. In yeast cells lacking Tdh2p, decreasing the levels of its functionally redundant homolog Tdh3p inhibited TBSV replication and resulted in equivalent levels of (+) and minus-stranded [(-)] viral RNA, in contrast to the hallmark excess of (+)RNA. Tdh2p specifically bound an AU pentamer sequence in the (-)RNA, suggesting that GAPDH promotes asymmetric RNA synthesis by selectively retaining the (-)RNA template in the replicase complex. Downregulation of GAPDH in a natural plant host decreased TBSV genomic RNA accumulation. Thus, TBSV co-opts the RNA-binding function of a metabolic protein, helping convert the host cell into a viral factory.

AB - Tomato bushy stunt virus (TBSV), a plus-stranded [(+)] RNA plant virus, incorporates the host metabolic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) into the viral replicase complex. Here, we show that, during TBSV replication in yeast, the yeast GAPDH Tdh2p moves from the cytosol to the peroxisomal membrane surface, the site of viral RNA synthesis. In yeast cells lacking Tdh2p, decreasing the levels of its functionally redundant homolog Tdh3p inhibited TBSV replication and resulted in equivalent levels of (+) and minus-stranded [(-)] viral RNA, in contrast to the hallmark excess of (+)RNA. Tdh2p specifically bound an AU pentamer sequence in the (-)RNA, suggesting that GAPDH promotes asymmetric RNA synthesis by selectively retaining the (-)RNA template in the replicase complex. Downregulation of GAPDH in a natural plant host decreased TBSV genomic RNA accumulation. Thus, TBSV co-opts the RNA-binding function of a metabolic protein, helping convert the host cell into a viral factory.

KW - CELLBIO

KW - MICROBIO

UR - http://www.scopus.com/inward/record.url?scp=40149092139&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=40149092139&partnerID=8YFLogxK

U2 - 10.1016/j.chom.2008.02.005

DO - 10.1016/j.chom.2008.02.005

M3 - Article

C2 - 18329617

AN - SCOPUS:40149092139

SN - 1931-3128

VL - 3

SP - 178

EP - 187

JO - Cell Host and Microbe

JF - Cell Host and Microbe

IS - 3

ER -

Tomato bushy stunt virus Co-Opts the RNA-Binding Function of a Host Metabolic Enzyme for Viral Genomic RNA Synthesis

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this