Olfactory receptor neurons prevent dissemination of neurovirulent influenza A virus into the brain by undergoing virus-induced apoptosis
Olfactory receptor neurons prevent dissemination of neurovirulent influenza A virus into the brain by undergoing virus-induced apoptosis
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DOI：
10.1099/0022-1317-83-9-2109
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发表时间：
2002-09-01
影响因子：
3.8
通讯作者：
Kimura, Y
中科院分区：
文献类型：
--
作者：
Mori, I;Goshima, F;Kimura, Y
鼻内接种甲型流感病毒的R404 BP株后，嗅觉受体神经元（ORN）被感染。病毒感染的神经元和一小部分邻近的未感染的神经元显示凋亡神经变性证实的活化caspase-3分子的免疫组化和末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法。然而，病毒感染仅限于外周神经上皮细胞内，所有小鼠均在感染后存活。病毒感染的ORN显示Fas配体分子的表达上调，激活c-Jun N-末端激酶信号转导途径。此外，lba 1表达活化的小胶质细胞/巨噬细胞似乎参与吞噬活动，最终清除凋亡小体。这些结果提出了一种可能性，即在感染早期诱导嗅觉受体神经元凋亡可能会对神经毒力病毒从外周侵入中枢神经系统产生保护作用。
Olfactory receptor neurons (ORNs) were infected upon intranasal inoculation with the R404BP strain of neurovirulent influenza A virus. Virus-infected neurons and a small fraction of neighbouring uninfected neurons displayed apoptotic neurodegeneration substantiated by the immunohistochemistry for activated caspase-3 molecules and the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling method. However, virus infection was restricted within the peripheral neuroepithelium and all mice survived the infection. Virus-infected ORNs revealed upregulated expression of the Fas ligand molecules, activating the c-Jun N-terminal kinase signal transduction pathway. In addition, lba1-expressing activated microglia/macrophages appeared to partake in phagocytic activities, eventually clearing apoptotic bodies. These results raise the possibility that induction of apoptosis in olfactory receptor neurons at an early stage of infection may provide protective effects against invasion of the neurovirulent virus from the peripheral to the CNS.