Suja M S, Mahadevan Anita, Madhusudana S N, Shankar S K
Department of Neuropathology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore 560 029, India.
Patholog Res Int. 2011;2011:374286. doi: 10.4061/2011/374286. Epub 2011 Aug 25.
To evaluate the role of apoptosis in rabies encephalitis in humans and canines infected with wild-type street virus, in comparison with rodent model infected with street and laboratory passaged CVS strain, we studied postmortem brain tissue from nine humans, six canines infected with street rabies virus, and Swiss albino mice inoculated intramuscularly (IM) and intracerebrally (IC) with street and CVS strains. Encephalitis and high rabies antigen load were prominent in canine and human brains compared to rodents inoculated with street virus. Neuronal apoptosis was detectable only in sucking mice inoculated with CVS strain and minimal in street virus inoculated mice. In a time point study in suckling mice, DNA laddering was noted only terminally (7 days p.i.) following IC inoculation with CVS strain but not with street virus. In weanling and adult mice, apoptosis was restricted to inflammatory cells and absent in neurons similar to human and canine rabies-infected brains. Absence of neuronal apoptosis in wild-type rabies may facilitate intraneuronal survival and replication while apoptosis in inflammatory cells prevents elimination of the virus by abrogation of host inflammatory response.
为了评估凋亡在感染野生型街毒株的人类和犬类狂犬病脑炎中的作用，并与感染街毒株和实验室传代CVS毒株的啮齿动物模型进行比较，我们研究了9例人类、6例感染街狂犬病病毒的犬类以及经肌肉注射（IM）和脑内注射（IC）接种街毒株和CVS毒株的瑞士白化小鼠的死后脑组织。与接种街病毒的啮齿动物相比，脑炎和高狂犬病抗原负荷在犬类和人类大脑中更为突出。仅在接种CVS毒株的乳鼠中可检测到神经元凋亡，而在接种街病毒的小鼠中凋亡极少。在对乳鼠的时间点研究中，仅在脑内接种CVS毒株后终末期（感染后7天）观察到DNA梯状条带，而接种街病毒后未观察到。在断奶小鼠和成年小鼠中，凋亡仅限于炎症细胞，神经元中不存在凋亡，这与人类和犬类狂犬病感染的大脑相似。野生型狂犬病中神经元凋亡的缺失可能有助于病毒在神经元内存活和复制，而炎症细胞中的凋亡通过消除宿主炎症反应来阻止病毒的清除。
