Association between human cytomegalovirus infection and histone acetylation level in various histological types of glioma

At present, glioma is the most common intracranial tumor and accounts for 40–60% of intracranial tumors. Glioma is highly anaplastic and demonstrates invasive growth. Although considerable progression has been achieved in the treatment of malignant glioma, the prognosis of this disease remains poor. Over the previous decade, several studies have confirmed that human cytomegalovirus (HCMV) enhances the growth or survival of tumors. This is likely to occur through mechanisms distinct from those of classic tumor viruses, which express transforming viral oncoproteins in the majority of tumor cells. The immediate-early 2 protein (IE86; 86 kDa) of HCMV is a key regulator for viral replication and host cell proliferation. The present study aimed to identify the association between the acetylation level and HCMV IE86 expression in various histological types of glioma. Tissue samples were obtained from 60 patients with glioma, consisting of 25 patients with glioblastoma multiforme (GBM), 16 patients with anaplastic glioma and 19 patients with low-grade glioma, in addition to 9 tissue samples obtained from the normal cortex, which were used as the control. The in situ protein expression of IE86, which is encoded by the IE2 gene, activating transcription factor 5 (ATF5), P300, acetyl-histone H3K9 and acetyl-histone H3K14 was detected by immunohistochemistry. The mRNA levels of ATF5, IE2 and P300 were measured by reverse transcription-quantitative polymerase chain reaction in GBM, anaplastic glioma, low-grade glioma and normal cortex tissue specimens. The protein levels of ATF5, IE86, P300, acetyl-histone H3K9 and acetyl-histone H3K14 were assessed by western blot analysis in high-grade glioma, low-grade glioma and normal cortex tissues. Analysis of the expression of the proteins revealed that the excessive expression of the HCMV IE86 protein is associated with the malignancy degree and acetylation level in glioma. IE86 expression is also associated with ATF5, which is an anti-apoptotic protein that is highly expressed in malignant glioma, but not in normal brain tissues. The expression level of IE86 may demonstrate considerable importance for the evaluation of the malignancy degree of human gliomas and extensive application in diagnostic and therapeutic medicine.