In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 19, No. 4 ( 2023-4-14), p. e1011316-
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1011316
DOI:
10.1371/journal.ppat.1011316.g001
DOI:
10.1371/journal.ppat.1011316.g002
DOI:
10.1371/journal.ppat.1011316.g003
DOI:
10.1371/journal.ppat.1011316.g004
DOI:
10.1371/journal.ppat.1011316.g005
DOI:
10.1371/journal.ppat.1011316.g006
DOI:
10.1371/journal.ppat.1011316.g007
DOI:
10.1371/journal.ppat.1011316.s001
DOI:
10.1371/journal.ppat.1011316.s002
DOI:
10.1371/journal.ppat.1011316.s003
DOI:
10.1371/journal.ppat.1011316.s004
DOI:
10.1371/journal.ppat.1011316.s005
DOI:
10.1371/journal.ppat.1011316.s006
DOI:
10.1371/journal.ppat.1011316.s007
DOI:
10.1371/journal.ppat.1011316.s008
DOI:
10.1371/journal.ppat.1011316.s009
DOI:
10.1371/journal.ppat.1011316.s010
DOI:
10.1371/journal.ppat.1011316.s011
DOI:
10.1371/journal.ppat.1011316.s012
DOI:
10.1371/journal.ppat.1011316.s013
DOI:
10.1371/journal.ppat.1011316.s014
DOI:
10.1371/journal.ppat.1011316.s015
DOI:
10.1371/journal.ppat.1011316.s016
DOI:
10.1371/journal.ppat.1011316.s017
DOI:
10.1371/journal.ppat.1011316.s018
DOI:
10.1371/journal.ppat.1011316.s019
DOI:
10.1371/journal.ppat.1011316.s020
DOI:
10.1371/journal.ppat.1011316.s021
DOI:
10.1371/journal.ppat.1011316.s022
DOI:
10.1371/journal.ppat.1011316.s023
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2023
detail.hit.zdb_id:
2205412-1
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