Herpesvirus Entry Mediator and Nectin-1 Mediate Herpes Simplex Virus 1 Infection of the Murine Cornea
Herpesvirus Entry Mediator and Nectin-1 Mediate Herpes Simplex Virus 1 Infection of the Murine Cornea
复制标题
DOI：
10.1128/jvi.05445-11
复制
发表时间：
2011-10-01
影响因子：
5.4
通讯作者：
Longnecker, Richard
中科院分区：
文献类型：
--
作者：
Karaba, Andrew H.;Kopp, Sarah J.;Longnecker, Richard
单纯疱疹病毒1 （HSV-1）是一种普遍存在的人类病原体，通过受体介导的病毒包膜与宿主细胞膜融合进入细胞。单纯疱疹病毒的包膜糖蛋白gD必须与其中一个受体结合才能进入。最近对敲除（KO）小鼠的研究表明，gD受体疱疹病毒进入介质（HVEM）和nectin-1是HSV-2在小鼠阴道和大脑中的主要进入受体。连接蛋白-1对HSV-2的神经元传播至关重要，尤其是在大脑中。这些模型的感染不需要HVEM，但当HVEM和nectin-1都不存在时，感染完全被阻止。我们试图确定HSV-1在眼部感染模型中使用敲除小鼠的受体需求。野生型、HVEM KO、nectin-1 KO和HVEM/nectin-1双KO小鼠通过角膜刻痕感染，并监测感染的临床症状和病毒在各组织中的复制。我们报告HVEM或连接素-1必须存在于HSV-1角膜感染。此外，我们观察到HVEM KO和nectin-1 KO小鼠的感染都减弱了。这与在阴道和大脑中报道的HSV-2的研究结果相反，表明HSV的受体需求因接种途径和/或血清型而异。
Herpes simplex virus 1 (HSV-1) is a ubiquitous human pathogen that enters cells by the receptor-mediated fusion of the viral envelope with a host cell membrane. The envelope glycoprotein gD of HSV must bind to one of its receptors for entry to take place. Recent studies using knockout (KO) mice demonstrated that the gD receptors herpesvirus entry mediator (HVEM) and nectin-1 are the primary entry receptors for HSV-2 in the mouse vagina and brain. Nectin-1 was most crucial for the neuronal spread of HSV-2, particularly in the brain. HVEM was dispensable for infection in these models, but when both HVEM and nectin-1 were absent, infection was completely prevented. We sought to determine the receptor requirements of HSV-1 in an ocular model of infection using knockout mice. Wild-type, HVEM KO, nectin-1 KO, and HVEM/nectin-1 double-KO mice were infected via corneal scarification and monitored for clinical signs of infection and viral replication in various tissues. We report that either HVEM or nectin-1 must be present for HSV-1 infection of the cornea. Additionally, we observed that the infection was attenuated in both HVEM KO and nectin-1 KO mice. This is in contrast to what was reported for studies of HSV-2 in vagina and brain and suggests that receptor requirements for HSV vary depending on the route of inoculation and/or serotype.