Tenser R B, Edris W A, Hay K A
Department of Medicine (Neurology), Penn State University College of Medicine, Hershey 17033.
Virology. 1993 Aug;195(2):337-47. doi: 10.1006/viro.1993.1384.
Herpes simplex virus (HSV) is a common neurotropic virus, and latent infection of sensory ganglion neurons readily occurs in humans and in experimentally infected animals. During HSV latency, infectious virus and viral antigen are not detected, and HSV transcription is limited to specific RNA termed latency-associated transcript (LAT). In the present study, the effect of altered nervous system function on HSV latent infection was investigated in dorsal root ganglia (drg) of experimentally infected mice. Latent infection of lumbar drg was established by footpad inoculation of HSV. During latency, sciatic neurectomy was performed in order to modify the in vivo function of latently infected neurons, and HSV LAT and HSV DNA in drg were investigated. Neurectomy has been used in many neurobiological studies to alter neuronal RNA and protein expression. After neurectomy there was a marked decrease in the number of LAT-positive neurons and in the amount of ganglion LAT. This was determined by in situ and RNA (Northern) blot hybridization. The neurectomy-related decrease of HSV LAT was apparent 9-10 days after neurectomy and was more marked after 21 days. The decrease was noted both in drg latently infected with standard thymidine kinase-positive (TK+) HSV and in ganglia infected with mutant TK- HSV. Since TK- HSV is largely reactivation defective, it is concluded that the neurectomy-induced decrease of LAT was probably not the result of in vivo HSV reactivation. It is acknowledged, however, that abortive reactivation by TK- HSV may occur, and decrease of latency may have resulted from neuronal or other host mechanisms subsequent to this. In order to investigate residual HSV latency, in addition to viral transcription, HSV DNA in drg was evaluated by polymerase chain reaction techniques. Decrease of HSV DNA was noted after neurectomy in drg latently infected with either TK+ or TK- HSV. It is suggested that the decrease in LAT expression detected was due to the change in neuronal transcription which is part of the neurectomy-induced axon reaction. Decreased HSV LAT may have led to decreased HSV DNA and latency. The decrease in the molecular markers of HSV latency following neurectomy emphasized the importance of neuronal control mechanisms in the pathogenesis of HSV latent infection.
单纯疱疹病毒（HSV）是一种常见的嗜神经病毒，在人类和实验感染的动物中，感觉神经节神经元很容易发生潜伏感染。在HSV潜伏期间，检测不到传染性病毒和病毒抗原，HSV转录仅限于一种称为潜伏相关转录本（LAT）的特定RNA。在本研究中，在实验感染小鼠的背根神经节（DRG）中研究了神经系统功能改变对HSV潜伏感染的影响。通过足垫接种HSV建立腰段DRG的潜伏感染。在潜伏期间，进行坐骨神经切除术以改变潜伏感染神经元的体内功能，并研究DRG中的HSV LAT和HSV DNA。神经切除术已在许多神经生物学研究中用于改变神经元RNA和蛋白质表达。神经切除术后，LAT阳性神经元的数量和神经节LAT的量显著减少。这是通过原位和RNA（Northern）印迹杂交确定的。神经切除术后9-10天，与神经切除术相关的HSV LAT减少明显，21天后更明显。在潜伏感染标准胸苷激酶阳性（TK+）HSV的DRG和感染突变TK-HSV的神经节中均观察到这种减少。由于TK-HSV在很大程度上存在再激活缺陷，因此得出结论，神经切除术诱导的LAT减少可能不是体内HSV再激活的结果。然而，公认TK-HSV可能会发生流产再激活，潜伏期的缩短可能是由此引发的神经元或其他宿主机制导致的。为了研究残留的HSV潜伏情况，除了病毒转录外，还通过聚合酶链反应技术评估了DRG中的HSV DNA。在潜伏感染TK+或TK-HSV的DRG中，神经切除术后观察到HSV DNA减少。提示检测到的LAT表达降低是由于神经元转录的变化，这是神经切除术诱导的轴突反应的一部分。HSV LAT的降低可能导致HSV DNA减少和潜伏期缩短。神经切除术后HSV潜伏分子标志物的减少强调了神经元控制机制在HSV潜伏感染发病机制中的重要性。
