Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, 52900, Israel.
Departments of Ophthalmology and of Molecular Microbiology and Genetics, University of Pittsburgh, Pittsburgh, PA, 15213, USA.
Virology. 2024 Jul;595:110096. doi: 10.1016/j.virol.2024.110096. Epub 2024 Apr 30.
Herpes stromal keratitis is the leading cause of infectious blindness in the western world. Infection by HSV1 is most common, but VZV and hCMV also infect the cornea. Multiple models of HSV1 corneal infection exist, but none for VZV and hCMV because of their host specificity. Here, we used commercially available 3D human corneal epithelial equivalents (HCEE) to study infection by these herpesviruses. HCEE was infected by HSV-1 and hCMV without requiring scarification and resulted in spreading infections. Spread of HSV-1 infection was rapid, while that of hCMV was slow. In contrast, infections with VZV required damage to the HCEE and did not spread. Acyclovir dramatically reduced replication of HSV-1 in this model. We conclude that highly quality-controlled, readily available HCEE is a useful model to study human-restricted herpesvirus infection of the human corneal epithelium and for screening of antiviral drugs for treating HSK in an 3D model system.
单纯疱疹性基质角膜炎是西方世界导致感染性失明的主要原因。单纯疱疹病毒 1 型（HSV1）感染最为常见，但水痘带状疱疹病毒（VZV）和人巨细胞病毒（hCMV）也会感染角膜。存在多种 HSV1 角膜感染模型，但由于宿主特异性，VZV 和 hCMV 没有相应模型。在这里，我们使用市售的 3D 人角膜上皮等效物（HCEE）来研究这些疱疹病毒的感染。HSV-1 和 hCMV 无需划痕即可感染 HCEE，导致其感染扩散。HSV-1 感染的传播速度很快，而 hCMV 则很慢。相比之下，VZV 的感染需要破坏 HCEE，且不会扩散。阿昔洛韦在该模型中显著降低了 HSV-1 的复制。我们得出结论，高度质量控制、易于获得的 HCEE 是研究人类局限疱疹病毒感染人角膜上皮的有用模型，也是在 3D 模型系统中筛选治疗 HSK 的抗病毒药物的有用模型。
