The role of herpesviruses in brain tumor development




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Herpesviruses are suggested to be involved in cancer pathogenesis since several years. A recent study suggested HCMV to be involved in glioma development or progression, and other studies found an inverse correlation between previous VZV infection and glioblastoma pathogenesis. The present study was conducted to evaluate these assumptions. Brain tumor tissues from 76 gliomas, meningiomas, and acoustic neurinomas were obtained, together with 71 corresponding blood samples. Nested PCR and immunohistochemistry were performed using several protocols to assess the prevalence of HCMV DNA and proteins in brain tumor tissues, blood samples, and short-term cultures of brain tumor tissues. Additionally, the serological status of 71 brain tumor patients concerning the prevalence of IgM and IgG antibodies to HCMV, HSV, EBV, and VZV was analyzed. Furthermore, a questionnaire was developed to control for putative medical risk factors indicating herpesvirus infection or reactivation, and to control for other putative (mainly medical) risk factors in brain tumor development. None of the 76 brain tumor tissues was positive for HCMV molecules in any analysis performed. The conflicting results may be due to geographical differences in the prevalence of HCMV; however, very recent studies conducted in the US and in France confirmed the absence of any HCMV molecules in primary brain tumors. In general, the overall seroprevalences of IgG antibodies to HCMV, HSV, EBV and VZV in brain tumor patients were similar to those of the German population. However, the prevalences of anti-HSV and anti-EBV IgGs in glioma patients showed trends that resemble previous findings. Overall, the questionnaire did not provide evidence for viral infections being involved in brain tumor development. For some factors such as the occurrence of allergies, hearing impairments, and especially the frequent high-level contact to animals in meningioma patients (private and occupational), the results were indicative but not conclusive for an association with brain tumor pathogenesis, and further research may be needed to clarify these issues. In summary, considering the results from laboratory analyses and the results of the questionnaire, the hypothesis of an association between herpesviruses and the development or progression of brain tumors cannot be supported.




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