Mann Mary Anne, Knipe David M, Fischbach Gerald D, Fields Bernard N
Department of Biology, Northeastern University, 360 Huntington Avenue, Boston, Massachusetts 02115, USA.
Virology. 2002 Nov 25;303(2):222-31. doi: 10.1006/viro.2002.1699.
Neonatal but not adult mice are vulnerable to reovirus invasion of the central nervous system after peripheral inoculation. After hindlimb injection, type 3 reovirus travels via the sciatic nerve to replicate in spinal cord motor neurons before spread to the brain and development of lethal encephalitis. Here we provide ultrastructural evidence for direct reovirus invasion of unmyelinated neonatal motor nerve terminals within 2 h and replication in spinal cord motor neurons within 14 h after hindlimb injection of 1-day-old mice. In adult mice, resistance to reovirus lethality after intracranial (IC) injection correlates with the restriction of virus growth in cortical neurons. We found that neuroinvasion also is age dependent after intramuscular injection. Virus lethality and CNS infection decreased sharply during the first postnatal week, while lethality after IC injection continued for 2 additional weeks. Mice inoculated at 7 days of age with high virus doses suffered paralysis of the injected limb, but significant brain infection was not lethal. These results suggest that reovirus invasion of the neonatal CNS is restricted by several progressive age-dependent mechanisms.
新生小鼠而非成年小鼠在经外周接种后易受呼肠孤病毒侵袭中枢神经系统。后肢注射后，3型呼肠孤病毒经坐骨神经传播，在脊髓运动神经元中复制，然后扩散至大脑并引发致死性脑炎。在此，我们提供超微结构证据，表明在对1日龄小鼠后肢注射后2小时内，呼肠孤病毒可直接侵袭新生无髓运动神经末梢，并在14小时内在脊髓运动神经元中复制。在成年小鼠中，颅内（IC）注射后对呼肠孤病毒致死性的抵抗力与病毒在皮质神经元中的生长受限有关。我们发现，肌肉注射后神经侵袭也与年龄有关。出生后第一周内，病毒致死率和中枢神经系统感染率急剧下降，而IC注射后的致死率又持续了两周。7日龄小鼠接种高剂量病毒后，注射肢体出现麻痹，但严重的脑部感染并不致命。这些结果表明，呼肠孤病毒对新生中枢神经系统的侵袭受到几种与年龄相关的渐进机制的限制。
