The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Zhejiang Province, People's Republic of China.
Wenzhou Medical University, Zhejiang Province, People's Republic of China.
Biochem Biophys Res Commun. 2020 Nov 12;532(3):393-399. doi: 10.1016/j.bbrc.2020.08.060. Epub 2020 Aug 31.
The HCMV (human cytomegalovirus) encodes numerous proteins which function to evade the immune response, which allows the virus to replicate. Exploring the mechanisms of HCMV immune escape helps to find the strategy to inhibit HCMV replicate. CD8 T cells play a critical role in the immune response to viral pathogens. However, the mechanisms of HCMV to evade the attack by CD8 T cells remain largely unknown. Viral CXCL1 (vCXCL1) is the production of HCMV UL146 gene. Here, we found that vCXCL1 promoted the resistance of hepatic cells to CD8 T cells. vCXCL1 increased the levels of PD-L1 protein expression and mRNA expression. VCXCL1 enhanced the binding of STAT3 transcription factor to the promoter of PD-L1 and increased the activity of PD-L1 promoter. Furthermore, down-regulation of PD-L1 reduced the effects of vCXCL1 on the resistance of hepatic cells to CD8 T cells. Taken together, vCXCL1 promotes the resistance of hepatic cells to CD8 T cells through up-regulation of PD-L1. This finding might provide a new mechanism of HCMV immune escape.
HCMV（人巨细胞病毒）编码许多蛋白质，这些蛋白质的功能是逃避免疫反应，从而允许病毒复制。探索 HCMV 免疫逃逸的机制有助于找到抑制 HCMV 复制的策略。CD8 T 细胞在针对病毒病原体的免疫反应中起着至关重要的作用。然而，HCMV 逃避 CD8 T 细胞攻击的机制在很大程度上尚不清楚。病毒 CXCL1（vCXCL1）是 HCMV UL146 基因的产物。在这里，我们发现 vCXCL1 促进了肝细胞对 CD8 T 细胞的抵抗。vCXCL1 增加了 PD-L1 蛋白表达和 mRNA 表达水平。VCXCL1 增强了 STAT3 转录因子与 PD-L1 启动子的结合，并增加了 PD-L1 启动子的活性。此外，下调 PD-L1 减少了 vCXCL1 对肝细胞对 CD8 T 细胞的抵抗作用。总之，vCXCL1 通过上调 PD-L1 促进了肝细胞对 CD8 T 细胞的抵抗。这一发现可能为 HCMV 免疫逃逸提供了新的机制。
