The Herpes Simplex Virus 1 vhs Protein Enhances Translation of Viral True Late mRNAs and Virus Production in a Cell Type-Dependent Manner
The Herpes Simplex Virus 1 vhs Protein Enhances Translation of Viral True Late mRNAs and Virus Production in a Cell Type-Dependent Manner
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DOI：
10.1128/jvi.00115-11
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发表时间：
2011-06-01
影响因子：
5.4
通讯作者：
Smiley, James R.
中科院分区：
文献类型：
--
作者：
Dauber, Bianca;Pelletier, Jerry;Smiley, James R.
单纯疱疹病毒1 （HSV-1）病毒粒子宿主关闭蛋白（vhs）降解病毒和细胞mrna。在这里，我们首次证明了vhs也以细胞类型依赖的方式促进病毒真正晚期mrna的翻译，并且这种作用决定了病毒在各自细胞类型中的生长表型。我们的研究是由于在感染vhs突变体的细胞中检测到胁迫颗粒，即翻译起始停滞的指标，而在野生型病毒感染的细胞中没有检测到。真正晚期基因产物gC和US11的积累在没有vhs的HeLa细胞和其他一些限制性细胞系中明显减少，但在Vero和其他允许细胞中没有，并且不依赖于真核起始因子2 (eIF2 α) α亚基的磷酸化。多体分析表明，在vhs-null病毒感染的HeLa细胞中，gC和US11转录本翻译不佳，而细胞mRNA的翻译不受影响。有趣的是，一种eIF4A抑制剂hippuristol在感染了野生型HSV-1的HeLa细胞中产生了类似的表型，而Vero细胞对该抑制剂的抗性要强得多。这些结果表明，真正的晚期基因转录物的翻译对翻译因子有限的条件特别敏感，而vhs能够在这些条件下阻止限制条件或促进翻译起始。细胞系对无vhs感染的不同容忍度可能源于翻译机制的恢复能力或控制mrna积累能力的差异。
The herpes simplex virus 1 (HSV-1) virion host shutoff protein (vhs) degrades viral and cellular mRNAs. Here, we demonstrate for the first time that vhs also boosts translation of viral true late mRNAs in a cell type-dependent manner and that this effect determines the viral growth phenotype in the respective cell type. Our study was prompted by the detection of stress granules, indicators of stalled translation initiation, in cells infected with vhs mutants but not in wild-type-virus-infected cells. Accumulation of true late-gene products gC and US11 was strongly reduced in the absence of vhs in HeLa cells and several other restrictive cell lines but not in Vero and other permissive cells and was independent of phosphorylation of the alpha subunit of eukaryotic initiation factor 2 (eIF2 alpha). Polysome analysis showed that gC and US11 transcripts were poorly translated in vhs-null-virus-infected HeLa cells, while translation of a cellular mRNA was not affected. Interestingly, hippuristanol, an eIF4A inhibitor, produced a similar phenotype in HeLa cells infected with wild-type HSV-1, while Vero cells were much more resistant to the inhibitor. These results suggest that translation of true late-gene transcripts is particularly sensitive to conditions of limited access to translation factors and that vhs is able either to prevent the limiting conditions or to facilitate translation initiation under these conditions. The varied permissivity of cell lines to vhs-null infection may stem from differences in the resilience of the translation machinery or the ability to control the accumulation of mRNAs.