Infection of neurons and encephalitis after intracranial inoculation of herpes simplex virus requires the entry receptor nectin-1
Infection of neurons and encephalitis after intracranial inoculation of herpes simplex virus requires the entry receptor nectin-1
复制标题
DOI：
10.1073/pnas.0908892106
复制
发表时间：
2009-10-20
影响因子：
11.1
通讯作者：
Spear, Patricia G.
中科院分区：
文献类型：
--
作者：
Kopp, Sarah J.;Banisadr, Ghazal;Spear, Patricia G.
多进入受体可以介导单纯疱疹病毒（HSV）对细胞的感染，从而允许感染和疾病的替代途径。我们研究了两种已知的进入受体，疱疹病毒进入介质（HVEM）和nectin-1，在中枢神经系统的神经元感染和脑炎的发展中的作用。用HSV接种野生型、HVEM KO、nectin-1 KO和HVEM/nectin-1双KO小鼠到海马中。检查小鼠的脑炎发展，或在接种后的不同时间处死小鼠，用于脑切片的免疫组织学分析。Nectin-1 KO小鼠在颅内接种后未显示疾病体征，并且在脑实质中未检测到HSV抗原。然而，HSV抗原检测到非实质细胞内衬脑室。在双KO小鼠中，即使在非实质细胞中也没有疾病和病毒抗原的可检测表达，表明这些细胞在nectin-1 KO小鼠中的感染依赖于HVEM的表达。野生型和HVEM KO小鼠迅速发展为脑炎，并且HSV在脑中的复制模式难以区分。因此，nectin-1的表达对于通过颅内途径的HSV感染和脑炎是必需的; HVEM在很大程度上是不相关的。这些结果与最近的发现形成对比，即（i）HVEM或nectin-1可以允许小鼠阴道上皮的HSV感染，和（ii）nectin-1不是能够使HSV感染从阴道上皮扩散到PNS和CNS的唯一受体。
Multiple entry receptors can mediate infection of cells by herpes simplex virus (HSV), permitting alternative pathways for infection and disease. We investigated the roles of two known entry receptors, herpesvirus entry mediator (HVEM) and nectin-1, in infection of neurons in the CNS and the development of encephalitis. Wild-type, HVEM KO, nectin-1 KO, and HVEM/nectin-1 double KO mice were inoculated with HSV into the hippocampus. The mice were examined for development of encephalitis or were killed at various times after inoculation for immunohistological analyses of brain slices. Nectin-1 KO mice showed no signs of disease after intracranial inoculation, and no HSV antigens were detectable in the brain parenchyma. However, HSV antigens were detected in non-parenchymal cells lining the ventricles. In the double KO mice, there was also no disease and no detectable expression of viral antigens even in non-parenchymal cells, indicating that infection of these cells in the nectin-1 KO mice was dependent on the expression of HVEM. Wild-type and HVEM KO mice rapidly developed encephalitis, and the patterns of HSV replication in the brain were indistinguishable. Thus, expression of nectin-1 is necessary for HSV infection via the intracranial route and for encephalitis; HVEM is largely irrelevant. These results contrast with recent findings that (i) either HVEM or nectin-1 can permit HSV infection of the vaginal epithelium in mice and (ii) nectin-1 is not the sole receptor capable of enabling spread of HSV infection from the vaginal epithelium to the PNS and CNS.