ICP27 Selectively Regulates the Cytoplasmic Localization of a Subset of Viral Transcripts in Herpes Simplex Virus Type 1-Infected Cells
ICP27 Selectively Regulates the Cytoplasmic Localization of a Subset of Viral Transcripts in Herpes Simplex Virus Type 1-Infected Cells
复制标题
DOI：
10.1128/jvi.78.1.23-32.2004
复制
发表时间：
2004-01
影响因子：
5.4
通讯作者：
A. Pearson;D. Knipe;D. Coen
中科院分区：
文献类型：
--
作者：
A. Pearson;D. Knipe;D. Coen
摘要有证据表明单纯疱疹病毒调节蛋白ICP 27介导病毒转录物的核输出;然而，在感染过程中这种活性的程度尚不清楚。ICP 27是有效表达长的、有渗漏的晚期UL 24转录物所必需的，但不是短的、早期UL 24转录物所必需的。我们发现，感染的ICP 27无效突变体导致检测不到的UL 24蛋白的表达，这代表了至少70倍的下降相对于野生型病毒。由于ICP 27的缺乏对UL 24蛋白水平的影响大于对转录物的影响，因此我们检查了其对UL 24转录物的亚细胞定位的影响。在野生型感染的细胞中，短和长的UL 24转录物主要与细胞质分离。然而，在不存在ICP 27的情况下，大于50%的长UL 24转录物是细胞核的，而细胞质的短UL 24转录物的百分比没有降低。这些结果也意味着短的UL 24转录本翻译不良。ICP 27对长UL 24转录物的细胞质定位的影响没有延伸到与其共享共同3′端的其他转录物或其他测试的转录物，包括gC和UL 42，其总体表达高度依赖于ICP 27。因此，ICP 27对mRNA积累和细胞质定位的双重作用并不总是相关的。这些结果鉴定了在感染期间依赖于ICP 27进行有效细胞质定位的病毒转录物，但它们也表明存在ICP 27独立的核输出途径，这些途径在感染期间可被许多病毒转录物访问。
ABSTRACT Evidence suggests that the herpes simplex virus regulatory protein ICP27 mediates the nuclear export of viral transcripts; however, the extent of this activity during infection is unclear. ICP27 is required for efficient expression of the long, leaky-late UL24 transcripts, but not for that of the short, early UL24 transcripts. We found that infection by an ICP27-null mutant resulted in undetectable UL24 protein expression, which represented at least a 70-fold decrease relative to that of wild-type virus. Because lack of ICP27 had a greater effect on levels of UL24 protein than on transcripts, we examined its effect on subcellular localization of UL24 transcripts. In wild-type-infected cells, both short and long UL24 transcripts fractionated predominantly with the cytoplasm. However, in the absence of ICP27, greater than 50% of long UL24 transcripts were nuclear, while the percentage of short UL24 transcripts that were cytoplasmic was not reduced. These results also imply that the short UL24 transcripts are translated poorly. The effect of ICP27 on cytoplasmic localization of the long UL24 transcripts did not extend to other transcripts with which it shared a common 3′ end or to other transcripts tested, including gC and UL42, whose overall expression is highly dependent on ICP27. Thus, the dual effects of ICP27 on mRNA accumulation and cytoplasmic localization are not always linked. These results identify viral transcripts that are dependent on ICP27 for efficient cytoplasmic localization during infection, but they also indicate the existence of ICP27-independent nuclear export pathways that are accessible to many viral transcripts during infection.