Japanese encephalitis virus infects neural progenitor cells and decreases their proliferation
Japanese encephalitis virus infects neural progenitor cells and decreases their proliferation
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DOI：
10.1111/j.1471-4159.2008.05511.x
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发表时间：
2008-08-01
影响因子：
4.7
通讯作者：
Basu, Anirban
中科院分区：
文献类型：
--
作者：
Das, Sulagna;Basu, Anirban
日本脑炎病毒（JEV）是人类，特别是儿童脑炎的常见原因，可导致大量神经元损伤。JEV感染的幸存者有严重的认知障碍，运动和行为障碍。我们推测，病毒对神经前体细胞（NPC）的消耗最终导致日本脑炎（JE）幸存者的神经系统后遗症。我们利用体内JEV感染模型和体外神经球培养来研究进行性JEV感染。通过流式细胞术测定细胞感染和细胞死亡。在动物和神经球中的BrdU给药用于确定NPC的增殖能力。JEV导致室下区（SVZ）活跃增殖的NPC群体的大量损失。JEV感染的脑室下区细胞形成神经球的能力严重受损。这可以归因于NPC中的JEV感染，然而，这不会导致有弹性的NPC细胞的稳健死亡。相反，JEV抑制这些细胞的循环能力，阻止它们的增殖。JEV主要针对出生后的关键年龄，并严重减少SVZ中的NPC池，从而损害损伤后的恢复过程。这种NPCs的生长和增殖抑制可能对乙脑幸存者的神经系统后果产生影响。
Japanese encephalitis virus (JEV), a common cause of encephalitis in humans, especially in children, leads to substantial neuronal injury. The survivors of JEV infection have severe cognitive impairment, motor and behavioral disorders. We hypothesize that depletion of neural progenitor cells (NPCs) by the virus culminates in neurological sequelae in survivors of Japanese encephalitis (JE). We utilized both in vivo model of JEV infection and in vitro neurosphere cultures to study progressive JEV infection. Cellular infection and cell death was determined by flow cytometry. BrdU administration in animals and in neurospheres was used to determine the proliferative ability of NPCs. JEV leads to massive loss of actively proliferating NPC population from the subventricular zone (SVZ). The ability of JEV infected subventricular zone cells to form neurospheres is severely compromised. This can be attributed to JEV infection in NPCs, which however do not result in robust death of the resilient NPC cells. Instead, JEV suppresses the cycling ability of these cells, preventing their proliferation. JEV primarily targets at a critical postnatal age and severely diminishes the NPC pool in SVZ, thus impairing the process of recovery after the insult. This arrested growth and proliferation of NPCs might have an effect on the neurological consequences in JE survivors.