Ogata A
Second Department of Pathology, Hokkaido University, School of Medicine, Sapporo, Japan.
Hokkaido Igaku Zasshi. 1990 Mar;65(2):221-34.
It is generally accepted that, the younger an animal is, the more susceptible it is to Japanese encephalitis virus (JEV) infection. A time-kinetic study of JEV antigen in the developing rat brain after infection disclosed that in the motor cortex, neurons were diffusely infected with JEV until the age of 5 days. However, on exposure from the 6th to 7th day, only the neurons of the upper layers were infected; those of the deeper layers remained uninfected. On the 8th day, the infection was limited to the superficial neurons, and from the 9th day onward, no neurons were infected. Since neuronal maturation in the motor cortex begins in the deeper layers and extends to the upper layers, it seems that JEV targets immature neurons. Fifteen-day-old rats, which were resistant to JEV infection, received intracerebral transplants of neurons taken from 19th-day embryos. When these animals were infected with JEV at 3 days after transplantation, viral antigen was detected only in the transplanted neurons; the host neurons were negative. However, when animals were infected with JEV at 9 days after transplantation, neither host neurons nor donor neurons became infected. This showed that JEV attacked embryonal neurons only early after transplantation into young-adult brains. JEV infectivity limited to the immature neurons was also confirmed by in vitro explant culture experiments. It can be concluded from these experiments that the susceptibility to JEV infection in the rat brain is closely associated with neuronal immaturity.
人们普遍认为,动物年龄越小,感染日本脑炎病毒(JEV)的易感性就越高。一项关于感染后发育中大鼠脑内JEV抗原的时间动力学研究表明,在运动皮层中,直到5日龄神经元都被JEV广泛感染。然而,在第6至7日暴露时,只有上层神经元被感染;深层神经元未被感染。在第8日,感染局限于表层神经元,从第9日起,没有神经元被感染。由于运动皮层中的神经元成熟从深层开始并延伸至上层,似乎JEV靶向未成熟神经元。对JEV感染有抵抗力的15日龄大鼠接受了取自19日龄胚胎的神经元脑内移植。当这些动物在移植后3天感染JEV时,仅在移植的神经元中检测到病毒抗原;宿主神经元呈阴性。然而,当动物在移植后9天感染JEV时,宿主神经元和供体神经元均未被感染。这表明JEV仅在移植到年轻成年大脑后的早期攻击胚胎神经元。体外器官培养实验也证实了JEV的感染性仅限于未成熟神经元。从这些实验可以得出结论,大鼠脑对JEV感染的易感性与神经元未成熟密切相关。