The substantia nigra is a major target for neurovirulent influenza A virus.
The substantia nigra is a major target for neurovirulent influenza A virus.
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DOI：
10.1084/jem.181.6.2161
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发表时间：
1995-06-01
期刊：
影响因子：
--
通讯作者：
Okada H
中科院分区：
文献类型：
--
作者：
Takahashi M;Yamada T;Nakajima S;Nakajima K;Yamamoto T;Okada H
在小鼠脑内接种甲型流感病毒神经毒性A/WSN/33 （H1N1； WSN）毒株、非神经毒性A/爱知/2/68 （H3N2；爱知）毒株以及它们之间的两种重组病毒后，进行了3-39 d的临床和免疫组织化学研究。编码神经氨酸酶WSN基因片段的病毒株诱导小鼠脑膜脑炎。R96毒株仅含有WSN毒株的神经氨酸酶基因，接种后小鼠症状轻微，脑膜区抗WSN抗体免疫染色弱阳性。含有WSN编码神经氨酸酶和基质蛋白基因片段的WSN和R404BP菌株在临床和病理上均具有明显的神经毒性。接种后第3天，在大鼠脑膜和室管膜区、脑室周围区神经元、大脑和小脑皮层、黑质致密带和腹侧被盖区检测到WSN抗原。在第7天，脑膜反应和神经元染色仍然可见，在黑质致密带和海马中明显有病毒抗原的晚期积累。双重免疫染色显示WSN抗原仅在神经元中可见，而在小胶质细胞和反应性星形胶质细胞中未见。凝集素maackia amurensis凝集素可识别甲型流感病毒在靶细胞膜上的结合位点Neu5Ac α 2,3 Gal序列，免疫染色显示阳性染色定位于腹侧黑质和海马。这些结果提示，神经毒性甲型流感病毒可能是脑后帕金森病的病原体之一。
Clinical and immunohistochemical studies were done for 3-39 d on mice after intracerebral inoculation with the neurovirulent A/WSN/33 (H1N1; WSN) strain of influenza A virus, the nonneurovirulent A/Aichi/2/68 (H3N2; Aichi) strain, and two reassortant viruses between them. The virus strains with the WSN gene segment coding for neuraminidase induced meningoencephalitis in mice. The mice inoculated with the R96 strain, which has only the neuraminidase gene from the WSN strain, had mild symptoms and weak positive immunostaining to the anti-WSN antibody in meningeal regions. Both the WSN and R404BP strains, which contain the WSN gene segments coding for neuraminidase and matrix protein, were clearly neurovirulent both clinically and pathologically. On day 3 after inoculation with either of these two strains, WSN antigen was detected in meningeal and ependymal areas, neurons of circumventricular regions, the cerebral and cerebellar cortices, the substantia nigra zona compacta, and the ventral tegmental area. On day 7, meningeal reactions and neuronal staining were still seen, and advanced accumulation of the viral antigen was evident in the substantia nigra zona compacta and hippocampus. Double immunostaining demonstrated that the WSN antigen was only seen in neurons and not in microglia or reactive astrocytes. Immunostaining for the lectin maackia amurensis agglutinin, which recognizes the Neu5Ac alpha 2,3 Gal sequence, which serves as a binding site for influenza A virus on target cell membranes, showed that positive staining was localized in the ventral substantia nigra and hippocampus. These results suggest that neurovirulent influenza A viruses could be one of the causative agents for postencephalitic parkinsonism.