Martin J R, Jenkins F J, Henken D B
Laboratory of Experimental Neuropathology, NINDS, NIH, Bethesda, MD 20892.
Acta Neuropathol. 1991;82(5):353-63. doi: 10.1007/BF00296546.
In animal models, spread of herpes simplex virus type 1 (HSV-1) from epithelial replication sites to the peripheral and central nervous system is known from analysis of individually dissected tissues. To examine virus spread in undissociated tissues, corneas of adult mice were inoculated with HSV-1. After 1 to 13 days groups of mice were perfused with formalin, and decalcified blocks of head and neck were embedded in paraffin. At intervals, serial sections were screened for HSV antigen. On days 1 and 2, viral antigen was restricted to cornea and conjunctiva but by days 3 and 4 was also seen in autonomic ganglia and the trigeminal system. On day 6, HSV antigen reached its maximum extent; infected sites included the trigeminal complex (ganglion, root, peripheral ophthalmic and maxillary branches and spinal nucleus and tract), ethmoid sinus and olfactory bulb, visual system, and autonomic ganglia (ciliary, pterygopalatine and superior cervical). Antigen progressively diminished on days 8 and 10, and was not detected on day 13. This method demonstrates a broader range of infected tissues and suggests a more complex pattern of HSV spread than has been previously recognized. Virus appears to reach the intracranial compartment by four different neural routes. When effects of higher and lower corneal inoculation doses were compared, a lower dose resulted in lower peak HSV titers in trigeminal ganglion and brain stem and later virus appearance in these tissues. Thus, dose may influence the kinetics of HSV spread from the peripheral inoculation site to the CNS.
在动物模型中，通过对单独解剖的组织进行分析，已知单纯疱疹病毒1型（HSV-1）可从上皮复制部位扩散至外周和中枢神经系统。为了检测病毒在未分离组织中的扩散情况，将HSV-1接种到成年小鼠的角膜上。在1至13天后，用福尔马林对小鼠组进行灌注，并将头颈脱钙块包埋在石蜡中。每隔一段时间，对连续切片进行HSV抗原筛查。在第1天和第2天，病毒抗原局限于角膜和结膜，但在第3天和第4天，在自主神经节和三叉神经系统中也可见到。在第6天，HSV抗原扩散范围达到最大；感染部位包括三叉神经复合体（神经节、神经根、外周眼支和上颌支以及脊髓核和束）、筛窦和嗅球、视觉系统以及自主神经节（睫状神经节、翼腭神经节和颈上神经节）。抗原在第8天和第10天逐渐减少，在第13天未检测到。该方法显示出更广泛的受感染组织范围，并提示HSV扩散模式比之前认识到的更为复杂。病毒似乎通过四种不同的神经途径到达颅内腔。比较较高和较低角膜接种剂量的影响时，较低剂量导致三叉神经节和脑干中的HSV峰值滴度较低，且病毒在这些组织中出现的时间较晚。因此，接种剂量可能会影响HSV从外周接种部位扩散至中枢神经系统的动力学。
