Type I Interferon Signaling Is Critical During the Innate Immune Response to HSV-1 Retinal Infection.
Type I Interferon Signaling Is Critical During the Innate Immune Response to HSV-1 Retinal Infection.
复制标题
DOI：
10.1167/iovs.63.13.28
复制
发表时间：
2022-12-01
影响因子：
4.4
通讯作者：
中科院分区：
文献类型：
--
作者：
急性视网膜坏死(ARN)是一种伴有致盲并发症的视网膜疱疹病毒感染。在这项研究中，我们试图创建一种可复制的ARN小鼠模型，模拟人类疾病，以更好地了解病毒感染期间视网膜内的先天免疫。C57BL/6J野生型(WT)和I型干扰素受体缺陷(IFNAR)−/−小鼠通过视网膜下注射不同数量的单纯疱疹病毒1型(HSV-1)。对WT组和IFNAR−/−组小鼠的病毒滴度、光学相干断层扫描(OCT)和眼底照相、脑炎发展和眼组织病理学进行评分，并进行比较。体内成像和组织病理学检查显示，WT小鼠的视网膜容易通过视网膜下注射感染HSV-1，导致视网膜白化和全层坏死。在IFNAR−/−小鼠中，单纯疱疹病毒1型诱导的视网膜病理与WT小鼠相比明显恶化，病毒滴度在感染后2天内显著升高，并持续到视网膜内感染后第5天。这些结果也在大脑中观察到，与WT小鼠相比，IFNAR−/−组的病毒滴度和脑炎频率明显更高。总而言之，这些发现表明，我们新的ARN小鼠模型模拟了人类疾病，可以用于研究视网膜内的先天免疫。我们得出结论，I型干扰素在将HSV-1局部控制在视网膜组织中并阻止其扩散到大脑中是至关重要的。
Acute retinal necrosis (ARN) is a herpesvirus infection of the retina with blinding complications. In this study, we sought to create a reproducible mouse model of ARN that mimics human disease to better understand innate immunity within the retina during virus infection. C57Bl/6J wild type (WT) and type I interferon receptor–deficient (IFNAR−/−) mice were infected with varying amounts of herpes simplex virus type 1 (HSV-1) via subretinal injection. Viral titers, optical coherence tomography (OCT) and fundus photography, the development of encephalitis, and ocular histopathology were scored and compared between groups of WT and IFNAR−/− mice. The retina of WT mice could be readily infected with HSV-1 via subretinal injection resulting in retinal whitening and full-thickness necrosis as determined by in vivo imaging and histopathology. In IFNAR−/− mice, HSV-1-induced retinal pathology was significantly worse when compared with WT mice, and viral titers were significantly elevated within two days after infection and persisted to day 5 after infection within the retina. These results were also observed in the brain where there were significantly higher viral titers and frequency of encephalitis in IFNAR−/− when compared to WT mice. Collectively, these findings show that our new mouse model of ARN mimics human disease and can be used to study innate immunity within the retina. We conclude that type I interferons are critical in containing HSV-1 locally within retinal tissues and prohibiting spread into the brain.
登录
查看更多内容
影响因子：
8
作者：
通讯作者：
--
影响因子：
5.4
作者：
Conrady, Christopher D.;Halford, William P.;Carr, Daniel J. J.
通讯作者：
Carr, Daniel J. J.
影响因子：
6.7
作者：
Guo, Hongyan;Koehler, Heather S.;Mocarski, Edward S.;Dix, Richard D.
通讯作者：
Dix, Richard D.
影响因子：
3.7
作者：
Al-Khatib, K;Williams, BRG;Carr, DJJ
通讯作者：
Carr, DJJ
影响因子：
4.4
作者：
Conrady, Christopher D.;Thapa, Manoj;Carr, Daniel J. J.
通讯作者：
Carr, Daniel J. J.