Inhibition of phospholipid biosynthesis decreases the activity of the tombusvirus replicase and alters the subcellular localization of replication proteins.
Inhibition of phospholipid biosynthesis decreases the activity of the tombusvirus replicase and alters the subcellular localization of replication proteins.
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DOI：
10.1016/j.virol.2011.04.008
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发表时间：
2011-07-05
期刊：
影响因子：
3.7
通讯作者：
Nagy PD
中科院分区：
文献类型：
--
作者：
Sharma M;Sasvari Z;Nagy PD
正链RNA病毒的复制依赖于细胞膜中存在的脂质。最近的全基因组筛选发现，8个磷脂合成基因影响番茄丛矮病毒（TBSV）在酵母模式宿主中的复制。为了测试磷脂在TBSV复制中的重要性，我们研究了其中一个鉴定的基因，即INO 2，它与Ino 4形成异二聚体，并且是参与调节磷脂生物合成的转录激活因子。INO 2的缺失或INO 2/INO 4的双缺失降低了TBSV的复制并抑制了病毒复制酶复合物的活性。此外，病毒复制蛋白的稳定性降低，病毒蛋白在ino 2 Δ ino 4 Δ酵母中的定位模式发生了显著变化。Opi 1是Ino 2和磷脂生物合成的阻遏物，过表达也抑制TBSV RNA积累。相反，Ino 2的过表达刺激TBSV RNA积累。我们还观察到对羊群房屋病毒（FHV）复制的抑制作用以及FHV复制蛋白在ino 2 Δ ino 4 Δ酵母中的稳定性降低。这些数据与磷脂在RNA病毒复制中的重要作用一致。
Replication of plus-strand RNA viruses depends on lipids present in cellular membranes. Recent genome-wide screens have revealed that eight phospholipid biosynthesis genes affected the replication of Tomato bushy stunt virus (TBSV) in yeast model host. To test the importance of phospholipids in TBSV replication, we studied one of the identified genes, namely INO2, which forms a heterodimer with Ino4, and is a transcription activator involved in regulation of phospholipid biosynthesis. Deletion of INO2, or double deletion of INO2/INO4, reduced TBSV replication and inhibited the activity of the viral replicase complex. In addition, the stability of the viral replication protein is decreased as well as the localization pattern of the viral protein changed dramatically in ino2Δ ino4Δ yeast. Over-expression of Opi1, a repressor of Ino2 and phospholipid biosynthesis, also inhibited TBSV RNA accumulation. In contrast, over-expression of Ino2 stimulated TBSV RNA accumulation. We also observed an inhibitory effect on Flock house virus (FHV) replication and the reduced stability of the FHV replication protein in ino2Δ ino4Δ yeast. These data are consistent with the important role of phospholipids in RNA virus replication.
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DOI：
10.1038/nrmicro1890
发表时间：
2008-05
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
Miller S;Krijnse-Locker J
通讯作者：
Krijnse-Locker J
影响因子：
6.7
作者：
Cherry S;Kunte A;Wang H;Coyne C;Rawson RB;Perrimon N
通讯作者：
Perrimon N
影响因子：
64.8
作者：
Krishnan, Manoj N.;Ng, Aylwin;Sukumaran, Bindu;Gilfoy, Felicia D.;Uchil, Pradeep D.;Sultana, Hameeda;Brass, Abraham L.;Adametz, Rachel;Tsui, Melody;Qian, Feng;Montgomery, Ruth R.;Lev, Sima;Mason, Peter W.;Koski, Raymond A.;Elledge, Stephen J.;Xavier, Ramnik J.;Agaisse, Herve;Fikrig, Erol
通讯作者：
Fikrig, Erol
影响因子：
30.3
作者：
Heaton NS;Randall G
通讯作者：
Randall G
影响因子：
6.7
作者：
Barajas D;Jiang Y;Nagy PD
通讯作者：
Nagy PD