Region of herpes simplex virus type 1 latency-associated transcript sufficient for wild-type spontaneous reactivation promotes cell survival in tissue culture
Region of herpes simplex virus type 1 latency-associated transcript sufficient for wild-type spontaneous reactivation promotes cell survival in tissue culture
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DOI：
10.1128/jvi.75.8.3636-3646.2001
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发表时间：
2001-04-01
影响因子：
5.4
通讯作者：
Jones, C
中科院分区：
文献类型：
--
作者：
Inman, M;Perng, GC;Jones, C
潜伏相关转录本（LAT）是唯一丰富的单纯疱疹病毒1型（HSV-1）在潜伏期表达的转录本。在兔眼模型中，LAT无效突变体不能有效地从潜伏期重新激活。我们最近证明，与LAT（+）菌株相比，LAT无效突变体dLAT 2903诱导感染兔三叉神经节中细胞凋亡水平增加（G. C.彭角作者：J.斯通，G。亨德森，A. Yokht，S. M. Slanina，F. M.霍夫曼，H。吉亚西A. B。Nesburn和C. S. Wechsler，Science 287：1500-1503，2000）。相同的研究还证明，表达LAT核苷酸301至2659的质粒在诱导细胞凋亡后增强了转染细胞的细胞存活。因此，我们假设LAT部分增强了自发再激活，因为它促进了受感染神经元的存活。在这里，我们报告了表达LAT 5'端不同部分的质粒在诱导凋亡后促进细胞存活的能力。（LAT核苷酸1至1499）促进neuro-2A细胞存活仅表达LAT的前811个核苷酸的质粒促进细胞存活的效率较低。表达LAT的前661个核苷酸或更少的质粒不能促进细胞存活。我们以前表明，一个突变体表达的LAT的前1.5 kb的野生型自发再激活兔，和一个突变体表达的LAT的前811个核苷酸的再激活频率高于dLAT 2903，但低于野生型病毒。此外，突变体在这里首次报道，仅表达LAT的前661或76个核苷酸，具有与LAT无效突变体dLAT 2903不可区分的自发再活化。总之，这些研究提供的证据表明，LAT促进细胞存活的能力与其增强自发再激活的能力之间存在功能关系。
The latency-associated transcript (LAT) is the only abundant herpes simplex virus type 1 (HSV-1) transcript expressed during latency. In the rabbit eye model, LAT null mutants do not reactivate efficiently from latency. We recently demonstrated that the LAT null mutant dLAT2903 induces increased levels of apoptosis in trigeminal ganglia of infected rabbits compared to LAT(+) strains (G.-C. Perng, C. Jones, J. Ciacci-Zarella, M. Stone, G. Henderson, A. Yokht, S. M. Slanina, F. M. Hoffman, H. Ghiasi, A. B. Nesburn, and C. S. Wechsler, Science 287:1500-1503, 2000). The same study also demonstrated that a plasmid expressing LAT nucleotides 301 to 2659 enhanced cell survival of transfected cells after induction of apoptosis. Consequently, we hypothesized that LAT enhances spontaneous reactivation in part, because it promotes survival of infected neurons. Here we report on the ability of plasmids expressing different portions of the 5' end of LAT to promote cell survival after induction of apoptosis, A plasmid expressing the first 1.5 kb of LAT (LAT nucleotides 1 to 1499) promoted cell survival in neuro-2A (mouse neuronal) and CV-1 (monkey fibroblast) cells, A plasmid expressing just the first 811 nucleotides of LAT promoted cell survival less efficiently. Plasmids expressing the first 661 nucleotides or less of LAT did not promote cell survival. We previously showed that a mutant expressing just the first 1.5 kb of LAT has wild-type spontaneous reactivation in rabbits, and a mutant expressing just the first 811 nucleotides of LAT has a reactivation frequency higher than that of dLAT2903 but lower than that of wild-type virus. In addition, mutants reported here for the first time, expressing just the first 661 or 76 nucleotides of LAT, had spontaneous reactivation indistinguishable from that of the LAT null mutant dLAT2903. In summary, these studies provide evidence that there is a functional relationship between the ability of LAT to promote cell survival and its ability to enhance spontaneous reactivation.