Mar. 24, 2009 Infection with human cytomegalovirus (HCMV) triggers expression of the telomerase reverse transcriptase (hTERT) gene in both normal human cells and tumor cells grown in culture.
HCMV has been suspected of causing or promoting cancer, but the mechanism by which the virus acts has been unclear. Several other cancer-related viruses stimulate telomerase activity, which promotes cell proliferation and immortalization.
To learn whether HCMV induces telomerase activity, Dawei Xu, M.D., Ph.D., of the Karolinska Institute in Stockholm, Sweden, and colleagues infected normal diploid fibroblasts and malignant glioma cells with HCMV or introduced a copy of the viral immediate early antigen 72 (IE-72) gene into the cells.
Infection with HCMV induced telomerase expression in both normal and malignant human cells. Introduction of the viral IE-72 gene also induced telomerase activity in both cell types.
"In this study, we reveal a novel mechanism through which HCMV may be linked to or modulate oncogenesis by demonstrating that HCMV stimulates hTERT transcription, thereby activating telomerase, which is essential for the immortalization and transformation of human cells," the authors write.
In an accompanying editorial, Jindrich Cinatl Jr., Ph.D., of the Universität Frankfurt in Germany and colleagues note that they hypothesized previously that HCMV may increase tumor malignancy rather than instigate malignancy. The results by Xu and colleagues may provide important mechanistic insight as to how such a modulatory role could occur.
"…HCMV-induced telomerase activation represents a mechanism that is of possible relevance for both (initiation of) malignant trans¬formation and oncomodulation by HCMV infection," the editorialists write.
The research is published in the March 24 online issue of the Journal of the National Cancer Institute.
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- Klas Strååt, Cheng Liu, Afsar Rahbar, Qingjun Zhu, Li Liu, Nina Wolmer-Solberg, Fenglan Lou, Zhaoxu Liu, Jie Shen, Jihui Jia, Satoru Kyo, Magnus Björkholm, Jan Sjöberg, Cecilia Söderberg-Nauclér, and Dawei Xu. Activation of Telomerase by Human Cytomegalovirus. Journal of the National Cancer Institute, 2009; DOI: 0.1093/jnci/djp031
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