登革病毒在中枢神经系统传播机制的研究

Dissemination of dengue virus in nervous system in mice

目的 分析登革 (DEN)病毒感染后中枢神经系统 (CNS)的病理变化及病毒在CNS内的传播方式。方法 用 2型登革病毒 (DEN 2 )对严重联合免疫缺陷 (SCID)小鼠进行脑内接种 ,电镜观察感染后不同时间 ,DEN病毒在CNS的分布、增殖及感染细胞的病变特点。结果 在感染早期 ,脊髓中央管上皮细胞胞浆内可见数量不等的病毒颗粒 ,随着感染的进展 ,子代病毒主要分布在神经元的粗面内质网和高尔基体内。在感染晚期 ,典型的神经突触及有髓和无髓的神经纤维中均可见病毒颗粒 ,其中有些病毒颗粒有与突触前膜融合倾向。在感染过程中 ,被感染的神经元逐渐出现空泡变性 ,进而溶解、死亡。结论 经脑内接种的登革病毒可能通过脑脊液播散 ,侵入脊髓灰质 ,并在神经元内增殖 ;并且 ,除组织间隙外 ,从神经元到神经元的传播途径可能参与登革病毒在CNS内的传播。

Objective To explore the transmission of dengue (DEN) virus in the central nervous system (CNS) and the pathogenesis of DEN infection in the system of mice. Methods Severe combined immunodeficient mice were intracerebrally inoculated with dengue virus type 2 (DEN 2). The distribution of the virus in CNS and ultrastructural pathomorphology of the infected cells were observed with electron microscopy after infection. Results DEN virions were seen in the cytoplasm of the ependymal cells in central canal in the early phase of the infection, and filial virus was mainly observed in lumen of rough endoplasmic reticulum (RER), RER vesicles and Golgi complex of infected neurons in the spinal cord. DEN 2 was also found in the myelinated, unmyelinated nerve fibers and typical synapse of the neurons during the late phase of the infection. Some vesicles containing viral particles appeared to fuse with the membrane of presynapse. During the infection, the neurons gradually showed vacuolation and death. Conclusion The results suggest that DEN virus, replicating in the neurons, disseminates to gray matter of the spinal cord via the cerebral spinal fluid and ependymal cells. Beside these kinds of transmission, neuron to neuron transport might be involved in it too.