Cytomegalovirus Shown to Cause Glioblastoma

 Human cytomegalovirus (hCMV) is part of the Herpesviridae family. It infects nearly half of the French population. Once infected, individuals are generally lifelong carriers of the virus, as is the case with all herpesviruses. The infection is often clinically asymptomatic. Viral transmission occurs through direct contact with the secretions of an infected person (eg, saliva, tears, urine, and feces). The virus can reactivate through occasional flare-ups.

Human Cytomegalovirus 

Increasing evidence identifies hCMV as a potential oncogenic virus. This virus is often detected in patients with cancer. Detection of the hCMV genome or antigens has been described in many malignant tumors, including breast, ovarian, colorectal, and prostate cancers.

Glioblastomas are the most common malignant primary tumors of the central nervous system (CNS). Glioblastoma multiforme (GBM) is the most frequent subtype of diffuse adult glioma. GBM remains an incurable disease. Despite aggressive treatment involving the most complete surgical resection possible and radiochemotherapy, the median overall survival of patients is only 15-18 months.

Hypotheses about the role of hCMV in GBM have been discussed for many years. The virus has indeed been found, albeit in very small quantities, in most GBM cases. It has been isolated from human neural stem cells, progenitor cells, and astrocytes. The latest World Health Organization classification of CNS tumors considers molecular information for the diagnostic classification and prognosis of gliomas. Although a link between hCMV and GBM has been established, causality has not been demonstrated.

Glioblastoma Development

A study conducted by researchers from the University of Bordeaux, University Hospital of Bordeaux, Besançon University Hospital, and University of Franche-Comté in Besançon, France, has shown, in an animal model, the role of hCMV in the development of glioblastoma. These findings were published in Cancer Gene Therapy in March 2024.

Initially, the researchers isolated hCMV from tumor biopsy samples (GBM) obtained from three patients during surgery. They also used the oncogenic high-risk strain HCMV-DB, which they had previously studied. Human brain astrocytes were infected in vitro with the isolated hCMV; within a few months, these infected cells transformed into cancer cells typical of GBM. These cells were then stereotactically implanted into the brains of immunosuppressed Ragγ2C-/- mice, leading to the formation of deadly glioblastomas in vivo.

For the first time, experimental proof of the generation of GBM cells induced by hCMV possessing characteristics like those of GBM and leading to the formation of a GBM in xenografted mice has been provided. According to the researchers, detection of hCMV in GBM biopsies could suggest use of anti-hCMV therapies, including antiviral treatment and immunotherapies targeted against hCMV antigens. New therapeutic strategies are necessary, and innovative experimental animal models need to be developed, they said.

According to the authors, these results "fit with an HCMV-induced glioblastoma model of oncogenesis in vivo, which will open the door to new therapeutic approaches and assess the anti-HCMV treatment as well as immunotherapy in fighting [GBM]."

https://www.medscape.com/viewarticle/cytomegalovirus-shown-cause-glioblastoma-2024a1000cvr