Center for Neurobiology and Vaccine Development, Ophthalmology Research, Department of Surgery, Cedars-Sinai Burns & Allen Research Institute, CSMC - SSB3, 8700 Beverly Blvd., Los Angeles, CA 90048, USA.
Viruses. 2024 Aug 29;16(9):1379. doi: 10.3390/v16091379.
CD80 is the best-known costimulatory molecule for effective T cell functions. Many different reports have summarized the role of CD80 in HSV-1 and its functions in maintaining adaptive immunity, which is the main player in causing herpes stromal keratitis (HSK). To determine the effects of absence or overexpression of CD80 in HSV-1 infection, we infected CD80 and WT mice with a recombinant HSV-1 expressing murine CD80 (HSV-CD80) in place of the latency associated transcript (LAT). Parental dLAT2903 virus lacking LAT was used as a control. After infection, critical components of infection like virus replication, eye disease, early cellular infiltrates into the corneas and trigeminal ganglia (TG), latency-reactivation in the infected mice were determined. Our findings reveal that the absence of CD80 in the CD80 mice infected with both viruses did not affect the viral titers in the mice eyes or eye disease, but it played a significant role in critical components of HSV-induced immunopathology. The WT mice infected with dLAT2903 virus had significantly higher levels of latency compared with the CD80 mice infected with dLAT2903 virus, while levels of latency as determined by gB DNA expression were similar between the WT and CD80 mice infected with HSV-CD80 virus. In contrast to the differences in the levels of latency between the infected groups, the absence of CD80 expression in the CD80 mice or its overexpression by HSV-CD80 virus did not have any effect on the time of reactivation. Furthermore, the absence of CD80 expression contributed to more inflammation in the CD80-infected mice. Overall, this study suggests that in the absence of CD80, inflammation increases, latency is reduced, but reactivation is not affected. Altogether, our study suggests that reduced latency correlated with reduced levels of inflammatory molecules and blocking or reducing expression of CD80 could be used to mitigate the immune responses, therefore controlling HSV-induced infection.
CD80 是最著名的协同刺激分子，可有效调节 T 细胞功能。许多不同的报告总结了 CD80 在 HSV-1 中的作用及其在维持适应性免疫中的功能，适应性免疫是引起疱疹性基质角膜炎（HSK）的主要因素。为了确定 CD80 在 HSV-1 感染中的缺失或过表达的影响，我们用表达鼠 CD80（HSV-CD80）的重组 HSV-1 感染 CD80 和 WT 小鼠，取代潜伏相关转录物（LAT）。缺乏 LAT 的亲本 dLAT2903 病毒被用作对照。感染后，通过检测病毒复制、眼部疾病、角膜和三叉神经节（TG）早期细胞浸润、感染小鼠的潜伏再激活等关键感染成分来确定。我们的研究结果表明，两种病毒感染的 CD80 缺失小鼠中 CD80 的缺失并不影响病毒在小鼠眼部的滴度或眼部疾病，但它在 HSV 诱导的免疫病理学的关键成分中发挥了重要作用。与 dLAT2903 病毒感染的 WT 小鼠相比，dLAT2903 病毒感染的 CD80 缺失小鼠潜伏水平显著升高，而 HSV-CD80 病毒感染的 WT 和 CD80 小鼠的潜伏水平通过 gB DNA 表达确定相似。与感染组潜伏水平的差异相反，CD80 缺失小鼠中 CD80 的缺失或 HSV-CD80 病毒的过表达对再激活时间没有任何影响。此外，CD80 缺失表达导致 CD80 感染小鼠的炎症增加。总的来说，这项研究表明，在没有 CD80 的情况下，炎症增加，潜伏减少，但再激活不受影响。总之，我们的研究表明，潜伏减少与炎症分子水平降低相关，阻断或减少 CD80 的表达可能用于减轻免疫反应，从而控制 HSV 引起的感染。
