人巨细胞病毒（HCMV）在胶质母细胞瘤（GBM）中的存在，且接受针对该病毒治疗的GBM患者预后有所改善，提示HCMV参与了GBM的进展。然而，尚未完全界定HCMV对GBM恶性表型贡献的统一机制。在这里，我们确定了SOX2，是一个神经胶质干细胞（GSC）的标志物，是细胞在胶质瘤中表达HCMV基因的关键决定因素。我们的研究表明，SOX2下调了早幼粒细胞白血病（PML）和Sp100，进而通过减少HCMV感染的胶质瘤细胞中的PML核小体数量促进病毒基因表达。相反，PML的表达对SOX2对HCMV基因表达的影响产生了对抗作用。此外，这种SOX2对HCMV感染的调控在GSC的神经元球测定和使用患者源性胶质瘤组织的移植瘤模型的小鼠异种移植中得到了证明。在这两种情况下，SOX2过表达促进了植入免疫缺陷小鼠的神经元球和异种移植的生长。最后，SOX2和HCMV即刻早期1（IE1）蛋白在胶质瘤患者的组织中的表达可以相关，有趣的是，SOX2和IE1水平的升高预测了更差的临床结果。这些研究表明，HCMV基因在胶质瘤中的表达是通过SOX2对PML表达的调节而调节的，而针对这个SOX2-PML途径中的分子可能会识别出胶质瘤治疗的治疗方法。版权所有：© 2023 Wen等。本文是根据知识共享署名许可证发布的开放式文章，在任何媒体上均可以自由地使用、分发和复制，前提是注明原作者和来源。

The presence of human cytomegalovirus (HCMV) in glioblastoma (GBM) and improved outcomes of GBM patients receiving therapies targeting the virus have implicated HCMV in GBM progression. However, a unifying mechanism that accounts for the contribution of HCMV to the malignant phenotype of GBM remains incompletely defined. Here we have identified SOX2, a marker of glioma stem cells (GSCs), as a key determinant of HCMV gene expression in gliomas. Our studies demonstrated that SOX2 downregulated promyelocytic leukemia (PML) and Sp100 and consequently facilitated viral gene expression by decreasing the amount of PML nuclear bodies in HCMV-infected glioma cells. Conversely, the expression of PML antagonized the effects of SOX2 on HCMV gene expression. Furthermore, this regulation of SOX2 on HCMV infection was demonstrated in a neurosphere assay of GSCs and in a murine xenograft model utilizing xenografts from patient-derived glioma tissue. In both cases, SOX2 overexpression facilitated the growth of neurospheres and xenografts implanted in immunodeficient mice. Lastly, the expression of SOX2 and HCMV immediate early 1 (IE1) protein could be correlated in tissues from glioma patients, and interestingly, elevated levels of SOX2 and IE1 were predictive of a worse clinical outcome. These studies argue that HCMV gene expression in gliomas is regulated by SOX2 through its regulation of PML expression and that targeting molecules in this SOX2-PML pathway could identify therapies for glioma treatment.Copyright: © 2023 Wen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.