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Review
. 2025 Jun 13;22(1):194.
doi: 10.1186/s12985-025-02826-3.

Role of cytomegalovirus in glioblastoma development: promoter or culprit?

Xiaoxin Wu #  1   2 , Zhengyu Zhang #  3 , Liang Zhang  4 , David J Daniels  5   6
Affiliations
Review

Role of cytomegalovirus in glioblastoma development: promoter or culprit?

Xiaoxin Wu et al. Virol J. .

Abstract

Glioblastoma is the most common primary malignant tumor of the central nervous system, with a median survival of less than two years. While the etiology of glioblastoma is unclear, viral infection has emerged as a potential contributing factor. Cytomegalovirus (CMV) was first reported to be associated with glioblastoma in 2002. Since then, many studies have detected CMV in glioblastoma tissues suggesting it may plays a role in the glioblastoma progression. While there is no direct evidence confirmings CMV as an oncogenic virus, studies have demonstrated that CMV promotes glioblastoma development in cell and animal models, with several CMV-related genes implicated in tumorigenesis. Importantly, adjuvant CMV antiviral therapy has been proven to improve glioblastoma patient survival. This review focuses on clinical studies regarding the relationship between CMV and glioblastoma, the mechanism of CMV in tumorigenesis, advances in animal models of CMV-induced glioblastoma, and key directions for future investigations.

Keywords: Cytomegalovirus; Etiology; Glioblastoma; Mechanism; Progress.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: We have got the publication licenses for Figs. 1, 2 and 3 from BioRender. Competing interests: The authors declare no competing interests. Conflict of interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Fig. 1
Fig. 1
Schematic diagram of the mechanisms by which cytomegalovirus promotes glioblastoma growth. CMV: Cytomegalovirus, MHC: Major histocompatibility complex. Created in BioRender. Wu, X. (2025) https://BioRender.com/t8sq5xn
Fig. 2
Fig. 2
Several lines of evidence support the role of cytomegalovirus in promoting glioblastoma development. A: Cytomegalovirus is detected in the tumors of patients with glioblastoma. B: CMV promotes glioblastoma progression in cell culture models. C: CMV promotes glioblastoma progression in a genetically engineered mouse model. Mut3 mouse: GFAP-cre; Nf1loxP/+; Trp53−/+ genetic mouse. CMV: Cytomegalovirus, GBM: Glioblastoma multiforme. Created in BioRender. Wu, X. (2025) https://BioRender.com/qqzub37
Fig. 3
Fig. 3
Schematic of an animal model for cytomegalovirus-induced glioblastoma under ideal conditions. A: Schematic of cytomegalovirus culture and in vivo and in vitro induction of glioblastoma diagram. B: Diagram of the construction of a cytomegalovirus transgenic mouse model. CMV: Cytomegalovirus. Created in BioRender. Wu, X. (2025) https://BioRender.com/bv3nsvz
See this image and copyright information in PMC

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