Relaxed repression of herpes simplex virus type 1 genomes in Murine trigeminal neurons.
Relaxed repression of herpes simplex virus type 1 genomes in Murine trigeminal neurons.
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小鼠三叉神经元中 1 型单纯疱疹病毒基因组的放松抑制。
DOI：
10.1128/jvi.01068-07
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发表时间：
2007
影响因子：
5.4
通讯作者：
DeLuca,NealA
中科院分区：
文献类型：
--
作者：
Terry-Allison,Tracy;Smith,ColtonA;DeLuca,NealA
在感觉神经元中缺乏病毒调节蛋白的情况下，单纯疱疹病毒（HSV）基因组的表达尚不清楚。此前，我们的研究小组报道了一种HSV即时早期（IE）突变体（d109），该突变体不能表达5种IE基因中的任何一种，并编码一种模型人巨细胞病毒即时早期启动子绿色荧光蛋白（GFP）转基因。在培养细胞中，仅在一小部分感染细胞中观察到该突变体表达的GFP。该亚群表现出细胞类型依赖性，因为gfp表达细胞的组分在检测的细胞类型中差异很大。在此，我们在小鼠胚胎三叉神经节（TG）培养中表征了这种突变体。我们发现d109对神经培养物无毒，并在培养物的整个生命周期中持续存在。与一些培养的细胞系和菌株不同，在令人惊讶的大子集神经元中观察到GFP转基因的表达。然而，很少有非神经元细胞表达GFP。我们还比较了ICP0和组蛋白去乙酰化酶抑制剂trichostatin A （TSA）激活非表达细胞中GFP表达的能力。在几乎所有细胞中，通过感染d105重新激活的静止基因组来提供ICP0，而TSA的再激活则更加有限，并且仅限于先前不表达的神经元。此外，我们发现不表达ICP0的d109在潜伏感染的成年TG培养物中持续地重新激活HSV 1型（KOS）。这些结果表明，在一些TG神经元中，持续存在的HSV基因组的状态可能比在非神经元细胞中观察到的更动态，更容易被激活。
The expression of herpes simplex virus (HSV) genomes in the absence of viral regulatory proteins in sensory neurons is poorly understood. Previously, our group reported an HSV immediate early (IE) mutant (d109) unable to express any of the five IE genes and encoding a model human cytomegalovirus immediate early promoter-green fluorescent protein (GFP) transgene. In cultured cells, GFP expressed from this mutant was observed in only a subset of infected cells. The subset exhibited cell type dependence, as the fractions of GFP-expressing cells varied widely among the cell types examined. Herein, we characterize this mutant in murine embryonic trigeminal ganglion (TG) cultures. We found that d109 was nontoxic to neural cultures and persisted in the cultures throughout their life spans. Unlike with some of the cultured cell lines and strains, expression of the GFP transgene was observed in a surprisingly large subset of neurons. However, very few nonneuronal cells expressed GFP. The abilities of ICP0 and an inhibitor of histone deacetylase, trichostatin A (TSA), to activate GFP expression from nonexpressing cells were also compared. The provision of ICP0 by infection with d105 reactivated quiescent genomes in nearly every cell, whereas reactivation by TSA was much more limited and restricted to the previously nonexpressing neurons. Moreover, we found that d109, which does not express ICP0, consistently reactivated HSV type 1 (KOS) in latently infected adult TG cultures. These results suggest that the state of persisting HSV genomes in some TG neurons may be more dynamic and more easily activated than has been observed with nonneuronal cells.