Abstract

BackgroundThe association between human cytomegalovirus (HCMV) and glioblastoma multiforme (GBM) is becoming a new concept. However, information on the geographic variability of HCMV prevalence in GBM remains scarce. Moreover, the potential roles of various viruses, such as polyomaviruses and oncogenic viruses, in gliomagenesis remain unclear. Our aim was to investigate the prevalence of HCMV in GBM among Japanese patients. Furthermore, this was the first study that evaluated infection with four new human polyomaviruses in GBMs. This study also provided the first data on the detection of human papillomavirus (HPV) in GBM in the Eastern world.MethodsWe measured the number of various viral genomes in GBM samples from 39 Japanese patients using real-time quantitative PCR. The tested viruses included HCMV, Merkel cell polyomavirus, human polyomavirus (HPyV) 6, HPyV7, HPyV9, Epstein–Barr virus, human herpesvirus 8, and HPV. Our quantitative PCR analysis led to the detection of eight copies of the HCMV DNA mixed with DNA extracted from 104 HCMV-negative cells. The presence of HCMV and HPV genomes was also assessed by nested PCR. Immunohistochemical study was also carried out to detect HPV-derived protein in GBM tissues.ResultsThe viral DNAs were not detectable, with the exception of HPV, which was present in eight out of 39 (21%) GBMs. All HPV-positive cases harbored high-risk-type HPV (HPV16 and HPV18). Moreover, the HPV major capsid protein was detected in GBM tumor cells.ConclusionsIn contrast with previous reports from Caucasian patients, we did not obtain direct evidence in support of the association between HCMV and GBM. However, high-risk-type HPV infection may play a potential etiological role in gliomagenesis in a subset of patients. These findings should prompt further worldwide epidemiological studies aimed at defining the pathogenicity of virus-associated GBM.

Highlights

  • The association between human cytomegalovirus (HCMV) and glioblastoma multiforme (GBM) is becoming a new concept

  • human papillomavirus (HPV) DNA was not detected in the non-neoplastic tissues, suggesting that that the HPV positivity resulted from HPV-infected GBM tumor cells

  • We explored for the first time the existence of four newly discovered human polyomaviruses, Merkel cell polyomavirus (MCPyV), human polyomavirus 6 (HPyV6), Human polyomavirus 7 (HPyV7), and Human polyomavirus (HPyV9), in GBMs

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Summary

Introduction

The association between human cytomegalovirus (HCMV) and glioblastoma multiforme (GBM) is becoming a new concept. Our aim was to investigate the prevalence of HCMV in GBM among Japanese patients This was the first study that evaluated infection with four new human polyomaviruses in GBMs. This study provided the first data on the detection of human papillomavirus (HPV) in GBM in the Eastern world. Several studies have indicated an exciting connection between human cytomegalovirus (HCMV) infection and glioblastoma multiforme (GBM), which is the most malignant primary brain tumor of human adults. In these studies, HCMV gene sequences were detected in >90%–.

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