经脑感染后登革病毒在小鼠脊髓分布特点的研究

Distribution of dengue virus in the spinal cord of mice after intracerebrally inoculation

目的 分析登革 (DEN)病毒在中枢神经系统 (CNS)内的生长规律和分布特点。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 ,应用空斑法和免疫荧光染色分别检测感染后小鼠CNS和血清中的病毒滴度及病毒抗原的分布。结果 感染后小鼠逐渐出现皮毛不整、脊柱侧凸及弛缓性麻痹。从感染后 3d到麻痹发生日 ,可在小鼠的脑皮质和脊髓中检测到滴度较高的DEN 2病毒 ,而血清中则检测不到病毒。免疫荧光染色显示DEN病毒抗原大量存在于大脑海马、基底核和脊髓灰质的神经元内。登革病毒抗原在感染早期和晚期在脊髓灰质的分布也存在差异。结论 感染后DEN在脊髓灰质内的分布不同提示脊髓不同部位的神经元对登革病毒的易感性可能不同。病毒在大脑、脊髓神经细胞内的增殖造成的细胞损害可能是登革病毒感染某些临床表现的病理基础。

Objective To investigate the replication rules and distributions of dengue (DEN) virus (and viral antigen) in the central nervous system. Methods Severe combined immunodeficient (SCID) mice were intracerebrally inoculated with dengue virus type 2 (DEN 2). The distribution of the virus was detected by using plaque assay and immunohistochemistry staining respectively. Results After inoculation, the mice showed ruffle and kyphoscoliosis and developed paralysis. A higher virus titer of DEN 2 was detected in the brain and spinal cord but not in the serum. DEN viral antigens were found predominately in the hippocampus and basal nuclei in the brain and in gray matter of the spinal cord. Interestingly, different distribution of DEN 2 virus in the spinal cord was noted at the early and late phase of the infection. Conclusion Dengue virus can replicate in the neurons and then lead to death of the neurons. The distribution of the virus in the spinal cord might be related to the different susceptibility of the neurons.