Tomato bushy stunt virus co-opts the RNA-binding function of a host metabolic enzyme for viral genomic RNA synthesis.
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.
Wang
Robert Yung-Liang
RY
Department of Plant Pathology, University of Kentucky, Lexington, KY 40546, USA.
Nagy
Peter D
PD
D001665:Binding Sites; D003600:Cytosol / Q000737:chemistry; D024202:Electrophoretic Mobility Shift Assay; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) / Q000378:metabolism*; D020675:Peroxisomes / Q000737:chemistry; D010940:Plant Proteins / Q000378:metabolism*; D011485:Protein Binding; D012367:RNA, Viral / Q000096:biosynthesis*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D012324:RNA-Dependent RNA Polymerase / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D014026:Nicotiana / Q000201:enzymology / Q000821:virology; D017864:Tombusvirus / Q000502:physiology*; D014779:Virus Replication
D010940:Plant Proteins; D012367:RNA, Viral; D016601:RNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating); C465225:TDH2 protein, S cerevisiae; D012324:RNA-Dependent RNA Polymerase