As an important immune cell, T lymphocytes can recognize the antigenic peptide through the specific T cell receptor on the cell surface, and activate the human acquired immune response. The diversity of T cell antigen recognition receptors determines the host immune response and disease prognosis. It has been reported that congenital Human cytomegalovirus (HCMV) infection causes the immune system to be suppressed in immunodeficient individuals. However, as an important protein of HCMV, whether IE2 plays a key role during HCMV latent infection and whether IE2 will change the TCR library is still unknown. The purpose of this study is discussed the effects of IE2 on TCR library and its diversity. First, UL122 genetically modified mice models that can steadily and continuously express IE2 protein were established. Then, we divided the transgenic mice into two groups, the experimental group (positive mice identified) and control group (negative mice, n=8 in each group). The establishment of UL122 genetically modified mice was identified by PCR technology. We used immunohistochemistry to detect the expression of IE2 in both groups. Flow cytometry was measured the proportion of CD4+ and CD8+T cells. High-throughput T cell receptor sequencing was performed to detect the differences of Vβ and Jβ gene segments and the change of TCR diversity. We found that IE2 was widely expressed in immune organs of experimental mice, and the expression of IE2 affects the distribution of CD4+ and CD8+ T cell. In addition, we first determined the profile of the TCRβ immune repertoire during HCMV latent infection, indicating that the expression of IE2 resulted in remarkably lower TCRβ diversity in peripheral blood T lymphocytes. Taken together, our data suggest that the expression of IE2 gives a rise to aberrant immune microenvironment that affects immune response, and the low diversity of TCR caused by IE2 expression may be a mechanism of HCMV immunosuppression.

人巨细胞病毒（human cytomegalovirus,HCMV）能诱导肿瘤细胞恶性转化且抑制肿瘤细胞凋亡,但HCMV编码的主要即刻早期调控蛋白IE86在这一过程中是否发挥关键作用仍然未知。为探究IE86对基因修饰荷胶质瘤小鼠p53表达水平及恶性胶质瘤细胞凋亡情况的影响,本研究通过PCR技术鉴定基因修饰小鼠IE86表达情况;实时定量PCR技术检测IE86和p53mRNA表达水平变化;免疫组织化学方法检测p53和p21蛋白的表达水平;TUNEL检测肿瘤组织细胞凋亡情况。结果显示,成功构建了IE86基因修饰小鼠模型;与IE86阴性组相比IE86阳性组p53表达水平上升（P＜0.05）,但p21表达水平下降（P＜0.05）;IE86阳性组细胞抗凋亡能力增强（P＜0.05）。以上结果表明,在基因修饰的小鼠中IE86持续表达但p53转录活性的指示标志p21下调,且IE86可提高恶性胶质瘤细胞抗凋亡能力。

Non-alcoholic fatty liver disease (NAFLD), a liver manifestation of metabolic syndrome, is associated with considerable health and socioeconomic burdens in many populations worldwide. Recent studies suggest that human cytomegalovirus (HCMV) infection might play a role in the pathogenesis of metabolic diseases, including NAFLD, but it is still unclear whether HCMV-encoded IE2 plays an important role in this process. Interestingly, SREBP1c was recently reported to play critical roles in the development of hepatic steatosis. In this study, we aimed to study the IE2 effect on the expression levels of SREBP1c and on lipid metabolism in the liver of UL122 genetically modified mice. First, UL122 genetically modified mice models that can steadily and continuously express IE2 protein were established. Then, the mice were divided into the experimental group (positive mice identified) and the control group (wild-type mice, n= 16 per group). The establishment of UL122 genetically modified mice was identified by PCR technology. The triglyceride content in their livers was measured using a colorimetric assay and oil red O-stain. Real-time PCR and immunohistochemistry were performed to detect the expression levels of SREBP1c mRNA and protein after HCMV infection. We found that SREBP1c expression was significantly elevated in the experimental group, and its overexpression in the liver cells can promote triglyceride accumulation and hepatic steatosis. Taken together, our data collectively demonstrate that HCMV infection is highly associated with NAFLD, SREBP1c overexpression promotes hepatic steatosis, and this up-regulation is most likely mediated by IE2.

Glioblastoma, the most common primary brain tumor of adults, is characterized by poor survival rates. Programmed death ligand 1 (PD-L1, CD274) has been implicated in the immune escape of glioblastoma. The presence of human cytomegalovirus (HCMV) in glioblastoma multiforme (GBM) has sparked considerable interest and controversy. The exposure of toll-like receptor 3 (TLR3) to pathogens induces an antiviral state in cells or in animals. In the current study, the expression of PD-L1 and TLR3 in HCMV-infected glioma specimens was observed to be higher compared to the control. We therefore investigated if PD-L1 expression in glioblastoma is mediated by TLR3 triggering in HCMV infected glioblastoma. TLR3 siRNA transfections were utilized to identify the induction of PD-L1 via TLR3 triggering in HCMV infected cell lines. Also, IL-8 and TGF-β were detected by ELISA for the antitumor role of TLR3. Thus, we propose a novel immune treatment using a combination of PD-L1 blockade with TLR3 triggering against HCMV infected glioblastoma.

Congenital HCMV infection has been reported to be involved in learning and memory impairment, but whether HCMV IE2 plays a key role in the process remains unknown. The purpose of this study was to study the effects of IE2 on the expression levels of NMDA receptors and CX43 in the hippocampal neurons of ul122 transgenic mice. Firstly, the ul122 genetically modified mice models that can steadily and continuously express IE2 protein were established. Then, the mice were divided into the experimental group (positive mice identified) and the control group (wild type mice. n = 24 in each group). The establishment of ul122 genetically modified mice was identified by PCR technology. The learning and memory ability were measured using the Morris water-maze test. Western blot and immunohistochemical study were performed to detect the expression level of Cx43 and NMDA receptors. The results of PCR indicated that the ul122 genetically modified model was successfully constructed. Morris water maze test result showed that in the experimental group, less platform crossings and Quadrant time (%) compared to the control group, but there was no difference in escape latency. The expression level of Cx43 in the hippocampus CA1 of the experimental group was significantly reduced in keeping with NMDA receptors in immunohistochemistry. The significant decreased expression level of Cx43 and NMDA receptors in the ul122 genetically modified mice hippocampus may be connection with the mechanism for spatial memory impairment.