Research Papers:
Human cytomegalovirus immediateearly protein promotes survival of glioma cells through interacting and acetylating ATF5
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Ming Hu1, Bin Wang1, Dongmeng Qian1, Mengyuan Wang2, Rui Huang1, Li Wei3, Ling Li1, Li Zhang1, David X. Liu4
1Department of Basic Medical Sciences, Qingdao University, Qingdao, China
2College of Life Sciences, Qingdao University, Qingdao, China
3The Hospital of People’s Liberation Army, Weifang, China
4Department of Pharmaceutical Sciences, Washington State University College of Pharmacy, Spokane, WA, USA
Correspondence to:
Bin Wang, email: [email protected]
Keywords: HCMV, IE86, glioma, ATF5, acetylation
Received: March 08, 2017 Accepted: April 03, 2017 Published: April 17, 2017
ABSTRACT
Human cytomegalovirus (HCMV), a widespread beta-herpes virus, infects a high percentage of gliomas. HCMV is specifically detected in human gliomas at a low level of expression raises the possibility that it may regulate the malignant phenotype in a chronic manner. Although HCMV is not recognized as an oncogenic virus, it might dysregulate signaling pathways involved in initiation and promotion of malignancy.
Here, our immunohistochemical staining reveals that nucleus staining of the HCMV 86-kDa immediate-early protein (IE86) is markedly increased in GBM (58.56%) compared with that in nontumorous samples (4.20%) and low-grade glioma(19.56%). IE86 staining positively correlates with the staining of activating transcription factor 5 (ATF5) which is essential for glioma cell viability and proliferation suggesting that HCMV IE86 could have important implications in glioma biology. Moreover, we find that the IE86 overexpression enhances glioma cell’s growth in vitro and in vivo. We demonstrate that IE86 protein physically interacts with, and acetylates ATF5 thereby promoting glioma cell survival. Therefore, our findings illustrate the biological significance of HCMV infection in accelerating glioma progression, and provide novel evidence that HCMV infection may serve as a therapeutic target in human glioma.