Zhang Xinyan, Xu Jinxian, Marshall Brendan, Dong Zheng, Smith Sylvia B, Zhang Ming
Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.
James and Jean Vision Discovery Institute, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.
Int J Mol Sci. 2021 Jul 29;22(15):8135. doi: 10.3390/ijms22158135.
(1) Background: caspase-12 is activated during cytomegalovirus retinitis, although its role is presently unclear. (2) Methods: (KO) or (WT) mice were immunosup eyes were analyzed by plaque assay, TUNEL assay, immunohistochemical staining, western blotting, and real-time PCR. (3) Results: increased retinitis and a more extensive virus spread were detected in the retina of infected eyes of KO mice compared to WT mice at day 14 p.i. Compared to MCMV injected WT eyes, mRNA levels of interferons α, β and γ were significantly reduced in the neural retina of MCMV-infected KO eyes at day 14 p.i. Although similar numbers of MCMV infected cells, similar virus titers and similar numbers of TUNEL-staining cells were detected in injected eyes of both KO and WT mice at days 7 and 10 p.i., significantly lower amounts of cleaved caspase-3 and p53 protein were detected in infected eyes of KO mice at both time points. (4) Conclusions: caspase-12 contributes to caspase-3-dependent and independent retinal bystander cell death during MCMV retinitis and may also play an important role in innate immunity against virus infection of the retina.
(1) 背景：巨细胞病毒性视网膜炎期间半胱天冬酶 - 12被激活，但其目前作用尚不清楚。(2) 方法：对基因敲除（KO）或野生型（WT）小鼠进行免疫抑制，通过噬斑测定、TUNEL测定、免疫组织化学染色、蛋白质印迹法和实时聚合酶链反应分析眼睛。(3) 结果：在感染后第14天，与野生型小鼠相比，基因敲除小鼠感染眼睛的视网膜中检测到视网膜炎增加且病毒传播更广泛。与注射巨细胞病毒的野生型眼睛相比，在感染后第14天，巨细胞病毒感染的基因敲除眼睛的神经视网膜中干扰素α、β和γ的mRNA水平显著降低。尽管在感染后第7天和第10天，基因敲除和野生型小鼠注射眼睛中检测到的巨细胞病毒感染细胞数量、病毒滴度和TUNEL染色细胞数量相似，但在这两个时间点，基因敲除小鼠感染眼睛中检测到的裂解型半胱天冬酶 - 3和p53蛋白量显著更低。(4) 结论：在巨细胞病毒性视网膜炎期间，半胱天冬酶 - 12通过半胱天冬酶 - 3依赖性和非依赖性途径促进视网膜旁观者细胞死亡，并且可能在针对视网膜病毒感染的固有免疫中也发挥重要作用。
