The comparative biology of latent herpes simplex virus type 1 and type 2 infections:: latency-associated transcript promoter activity and expression in vitro and in infected mice

The comparative biology of latent herpes simplex virus type 1 and type 2 infections:: latency-associated transcript promoter activity and expression in vitro and in infected mice
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DOI:
10.3109/13550289809113479
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发表时间:
1998-02-01
影响因子:
3.2
通讯作者:
Straus, SE
Straus, SE
中科院分区:
医学4区
文献类型:
--
作者:
Lekstrom-Himes, JA;Wang, KN;Straus, SE

文献摘要

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HSV-1和HSV-2表达丰富的潜伏相关转录物(LATs),没有这些转录物,这些病毒在动物中无效地再活化。为了进一步表征LATs的潜伏性HSV-1和-2感染的比较生物学的重要性,我们评估了病毒LAT启动子在体外使用瞬时转染试验的相对活动?和使用小鼠眼部感染模型的LAT体内积累。在体外,HSV-2 LAT启动子被证明在驱动报告基因表达方面比HSV-1启动子有效6至10倍。在小鼠中,HSV-1和HSV-2在眼睛中的病毒复制水平相当,但HSV-2在三叉神经节和大脑中的滴度高于HSV-1。定量竞争DNA和RNA(RT)PCR和原位杂交显示,潜伏感染HSV-2的神经节中含有6倍多的DNA拷贝(P=0.003),8倍多的LATS(P=0.01),和9倍多的LAT原位阳性神经元。然而,两种病毒每个潜伏基因组的LAT数量相等。虽然在瞬时表达测定中HSV-2 LAT启动子比HSV-1启动子更有效,但HSV-1和2 LAT在小鼠三叉神经节中的积累是相当的。
HSV-1 and HSV-2 express abundant latency-associated transcripts (LATs) without which these viruses reactivate in animals inefficiently. To further characterize the importance of LATs to the comparative biology of latent HSV-1 and -2 infections, we assessed the relative activities of the viral LAT promoters in vitro using transient transfection assays? and the accumulation of LATs in vivo using a mouse ocular infection model. In vitro, the HSV-2 LAT promoter proved to be six to tenfold more potent than the HSV-1 promoter in driving reporter gene expression. In mice HSV-1 and -2 achieved comparable levels of virus replication in the eye, but HSV-2, grew to higher titers than HSV-1 in trigeminal ganglia and brain. Quantitative-competitive DNA and RNA (RT) PCR and in situ hybridization showed that ganglia latently infected with HSV-2 contained sixfold more copies of DNA (P=0.003), eightfold more LATS (P=0.01), and ninefold more LAT in situ-positive neurons. However, the numbers of LATs per latent genome were equivalent for both viruses. Although the HSV-2 LAT promoter is more potent than the HSV-1 promoter in transient expression assays, the accumulation of HSV-1 and 2 LATs in mouse trigeminal ganglia is comparable.