West Nile virus-induced acute flaccid paralysis is prevented by monoclonal antibody treatment when administered after infection of spinal cord neurons
West Nile virus-induced acute flaccid paralysis is prevented by monoclonal antibody treatment when administered after infection of spinal cord neurons
复制标题
DOI：
10.1080/13550280801958930
复制
发表时间：
2008-01-01
影响因子：
3.2
通讯作者：
Diamond, Michael S.
中科院分区：
文献类型：
--
作者：
Morrey, John D.;Siddharthan, Venkatraman;Diamond, Michael S.
急性弛缓性脊髓灰质炎样麻痹发生在自然西尼罗河病毒（WNV）感染的动物和人类病例的子集。为了评价病理学和治疗干预的可能性，作者通过将WNV直接注射到仓鼠的坐骨神经或脊髓中来建立急性弛缓性麻痹模型。通过直接将西尼罗河病毒注射到神经系统的选定部位，作者将导致后肢瘫痪的病变定位到腰脊髓。免疫组织化学分析瘫痪仓鼠的脊髓切片显示，WNV感染的神经元主要定位于灰质的腹侧运动角，与脊髓灰质炎样临床表现一致。TUNEL（末端脱氧核苷酸转移酶介导的BrdUTP缺口末端标记）和胆碱乙酰转移酶染色，分别确定神经元凋亡和细胞功能下降。在脊髓直接感染西尼罗河病毒后2至3天，给予hE16（一种有效中和的人源化抗西尼罗河病毒单克隆抗体）可显著降低瘫痪和死亡率。此外，在坐骨神经接种WNV后5天单次注射hE16也防止了麻痹。总之，这些实验确定仓鼠中WNV诱导的急性弛缓性麻痹是由于腰脊髓中的神经元感染和损伤，并且当在脊髓神经元的WNV感染后施用时，用治疗性抗体治疗防止麻痹。
Acute flaccid polio-like paralysis occurs during natural West Nile virus (WNV) infection in a subset of cases in animals and humans. To evaluate the pathology and the possibility for therapeutic intervention, the authors developed a model of acute flaccid paralysis by injecting WNV directly into the sciatic nerve or spinal cord of hamsters. By directly injecting selected sites of the nervous system with WNV, the authors mapped the lesions responsible for hind limb paralysis to the lumbar spinal cord. Immunohistochemical analysis of spinal cord sections from paralyzed hamsters revealed that WNV-infected neurons localized primarily to the ventral motor horn of the gray matter, consistent with the polio-like clinical presentation. Neuronal apoptosis and diminished cell function were identified by TUNEL (terminal deoxynucleotidyl transferase-mediated BrdUTP nick end labeling) and choline acetyltransferase staining, respectively. Administration of hE16, a potently neutralizing humanized anti-WNV monoclonal antibody, 2 to 3 days after direct WNV infection of the spinal cord, significantly reduced paralysis and mortality. Additionally, a single injection of hE16 as late as 5 days after WNV inoculation of the sciatic nerve also prevented paralysis. Overall, these experiments establish that WNV-induced acute flaccid paralysis in hamsters is due to neuronal infection and injury in the lumbar spinal cord and that treatment with a therapeutic antibody prevents paralysis when administered after WNV infection of spinal cord neurons.