Changes to Euchromatin on LAT and ICP4 Following Reactivation Are More Prevalent in an Efficiently Reactivating Strain of HSV-1
Changes to Euchromatin on LAT and ICP4 Following Reactivation Are More Prevalent in an Efficiently Reactivating Strain of HSV-1
复制标题
HSV-1高效再活化株中LAT和ICP4上的外染色质在再活化后的变化更为普遍
DOI：
10.1371/journal.pone.0015416
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发表时间：
2010-11-04
期刊：
影响因子：
3.7
通讯作者：
Neumann, Donna M.
中科院分区：
文献类型：
--
作者：
Creech, Clinton C.;Neumann, Donna M.
背景资料：通过翻译后组蛋白修饰的表观遗传机制在感觉神经元中HSV-1基因组潜伏期的建立和维持中起作用。考虑到许多翻译后组蛋白标记在本质上是可逆的，表观遗传机制也可能在诱导HSV-1再活化的过程中发挥关键作用。方法学/主要发现：本研究利用经角膜离子导入肾上腺素（TCIE）诱导的HSV-1感染和再激活的兔眼模型，以表征在施加再活化刺激后0.5至4小时之间发生的染色质变化。我们的目标是探索染色质重塑是HSV-1再活化过程中早期和重要步骤的假设。对HSV-1潜伏感染的兔三叉神经节（TG）的分析表明，在HSV-1的高效再活化McKrae株中，到TCIE后1小时，常染标记H3 K4 me 2在LAT 5 '外显子区的富集显著降低（类似于2.5倍），在裂解性ICP 4启动子区的富集显著增加（类似于3倍）。与此相反，我们观察到，在TCIE后4小时内，与HSV-1的弱再活化科斯株的LAT 5 '外显子或ICP 4启动子区相关的H3 K4 me 2常染色质标记没有显著变化。这些观察到的表观遗传变化与转录活性相关的暗示通过在TCIE后检查LAT和裂解转录物丰度的qRT-PCR证实。我们发现，在HSV-1的McKrae株中，通过肾上腺素的离子电渗后2小时，LAT RNA的丰度显著降低，同时ICP 4的转录物丰度增加。通过比较，我们观察到没有变化的LAT或ICP 4转录丰度差的再激活剂科斯后，通过4小时的肾上腺素离子导入。结论/意义：我们的研究结果表明，染色质重塑是一个早期的和必要的步骤，在体内HSV-1的再激活过程中。
Background: Epigenetic mechanisms, via post-translational histone modifications, have roles in the establishment and maintenance of latency of the HSV-1 genome in the sensory neurons. Considering that many post-translational histone marks are reversible in nature, epigenetic mechanisms may also play a critical role in the process of induced HSV-1 reactivation.Methodology/Principal Findings: This study utilized the rabbit ocular model of HSV-1 infection and reactivation, induced by the transcorneal iontophoresis of epinephrine (TCIE), to characterize changes to chromatin that occur between 0.5 and 4 h following the application of the reactivation stimulus. Our goal was to explore the hypothesis that chromatin remodeling is an early and essential step in the process of HSV-1 reactivation. Analysis of the HSV-1 latently infected rabbit trigeminal ganglia (TG) showed that enrichment of the euchromatic marker H3K4me2 significantly decreased in the LAT 5'exon region (similar to 2.5-fold) and significantly increased in the lytic ICP4 promoter region (similar to 3-fold) by 1 h post-TCIE in the highly efficient reactivating McKrae strain of HSV-1. In contrast, we observed no significant change in the euchromatic marks of H3K4me2 associated with LAT 5'exon or ICP4 promoter regions of the poorly reactivating KOS strain of HSV-1 following TCIE through 4 h. The implication that these observed epigenetic changes were linked to transcriptional activity was confirmed by qRT-PCR examining both LAT and lytic transcript abundance following TCIE. We found a significant decrease in the abundance of LAT RNA by 2 h post-iontophoresis of epinephrine coupled to an increase in the transcript abundance of ICP4 in the McKrae strain of HSV-1. By comparison, we observed no change in the LAT or ICP4 transcript abundance of the poor reactivator KOS following iontophoresis of epinephrine through 4 h.Conclusions/Significance: Our results implicate that chromatin remodeling is an early and essential step involved in the process of in vivo HSV-1 reactivation.