血液通路在H5N1高致病性禽流感病毒入侵小鼠中枢神经系统中的作用

Role of blood pathway in the invasion of highly pathogenic H5N1 avian influenza virus into the central nervous system

摘要:

【目的】研究血液通路在H5N1高致病性禽流感病毒入侵小鼠中枢神经系统中的作用。【方法】用3株H5N1病毒滴鼻感染BALB/c小鼠，研究小鼠肺、脑、血中的病毒在感染后不同时间点的复制动态及病理进展，通过免疫组化和免疫荧光染色显示病毒在脑部血管内皮细胞及血管周围神经组织的感染情况。【结果】小鼠感染后病毒迅速在肺中高效复制，随即形成病毒血症；感染后第6天病毒在肺中的滴度和在血液样本中的检出率达到峰值，此时小鼠脑部才开始检测到病毒；小鼠脑内血管内皮细胞、脑血管周围神经组织的神经元和神经胶质细胞中可检测到流感病毒NP蛋白。【结论】血液播散可能是高致病性H5N1禽流感病毒进入中枢神经系统的途径之一。

Abstract:

[Objective] To investigate the role of blood dissemination in the invasion of the central nervous system by the highly pathogenic H5N1 influenza viruses. [Methods] Three H5N1 strains were intranasally inoculated into BALB/c mice to study the replication and pathogenic kinetics of the viruses in lung, brain, and blood. Infection of the brain vascular endothelial cells and nerve tissue around the blood vessels by the virus was investigated by immunohistochemistry and immunofluorescence staining techniques. [Results] Virus replicated efficiently in lungs, leading to viremia quickly after inoculation. At 6 d post inoculation, both the viral titre in lungs and the detection rate of viremia peaked; concomitantly, the viral NP (Nuclear protein) protein began to be detectable in the central nervous system. Viral NP proteins were observed in the brain vascular endothelial cells and in the neurons and astrocytes around blood vessels. [Conclusion] Blood dissemination could be one of the pathways through which the highly pathogenic H5N1 influenza invades the central nervous system.