Wang Robert Yung-Liang, Nagy Peter D
Department of Plant Pathology, University of Kentucky, Lexington, KY 40546, USA.
Cell Host Microbe. 2008 Mar 13;3(3):178-87. doi: 10.1016/j.chom.2008.02.005.
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.
番茄丛矮病毒（TBSV）是一种正链[（+）]RNA植物病毒，它将宿主代谢酶甘油醛-3-磷酸脱氢酶（GAPDH）纳入病毒复制酶复合体。在此，我们表明，在酵母中TBSV复制期间，酵母GAPDH Tdh2p从细胞质转移到过氧化物酶体膜表面，即病毒RNA合成的位点。在缺乏Tdh2p的酵母细胞中，降低其功能冗余同源物Tdh3p的水平会抑制TBSV复制，并导致正链[（+）]和负链[（-）]病毒RNA水平相当，这与标志性的过量（+）RNA形成对比。Tdh2p特异性结合（-）RNA中的一个AU五聚体序列，表明GAPDH通过在复制酶复合体中选择性保留（-）RNA模板来促进不对称RNA合成。在天然植物宿主中下调GAPDH会降低TBSV基因组RNA的积累。因此，TBSV利用一种代谢蛋白的RNA结合功能，帮助将宿主细胞转变为病毒工厂。
