Neuronal control of herpes simplex virus latency.
Neuronal control of herpes simplex virus latency.
复制标题
单纯疱疹病毒潜伏期的神经元控制。
作者：
Tenser,RB;Edris,WA;Hay,KA
单纯疱疹病毒（HSV）是一种常见的嗜神经病毒，潜伏感染的感觉神经节神经元容易发生在人类和实验感染的动物。在HSV潜伏期，感染性病毒和病毒抗原未被检测到，并且HSV转录仅限于称为潜伏相关转录物（LAT）的特异性RNA。在本研究中，神经系统功能的改变对HSV潜伏感染的实验感染小鼠的背根神经节（DRG）的影响进行了研究。通过足垫接种HSV建立腰背部潜伏感染。潜伏期行坐骨神经切除术，以改变潜伏感染神经元的在体功能，并检测DRG内HSV LAT和HSV DNA。神经切除术已被用于许多神经生物学研究，以改变神经元RNA和蛋白质表达。神经切除后，有一个显着的减少，在LAT阳性神经元的数量和神经节LAT的量。用原位RNA（北方）印迹杂交法测定。神经切除术后9-10天HSV LAT明显降低，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减少。由于TK-HSV在很大程度上是再激活缺陷的，因此可以得出结论，神经切除术诱导的LAT降低可能不是体内HSV再激活的结果。然而，公认的是，可能发生TK-HSV的失败再激活，并且潜伏期的减少可能是由随后的神经元或其他宿主机制引起的。为了研究残留的HSV潜伏期，除了病毒转录外，还通过聚合酶链反应技术评价drg中的HSV DNA。TK+或TK-HSV潜伏感染的DRG神经切除后HSV DNA均减少。这表明检测到的LAT表达的减少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降低可能导致HSV DNA和潜伏期减少。神经切除术后HSV潜伏期的分子标志物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。
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 thein vivofunction 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 byin situand 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 ofin vivoHSV 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.