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J Natl Cancer Inst. 2008 Jan 16;100(2):98-108. doi: 10.1093/jnci/djm269. Epub 2008 Jan 8.

Regulation of telomerase and telomeres: human tumor viruses take control.

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  • 1Department of Microbiology, Immunology, and Molecular Genetics, University of Kansas Medical Center, 3025 Wahl Hall West, 3901 Rainbow Blvd, Kansas City, KS 66160, USA.

Abstract

Human tumor viruses are responsible for one-fifth of all cancers worldwide. These viruses have evolved multiple strategies to evade immune defenses and to persist in the host by establishing a latent infection. Proliferation is necessary for pretumor cells to accumulate genetic alterations and to acquire a transformed phenotype. However, each cell division is associated with a progressive shortening of the telomeres, which can suppress tumor development by initiating senescence and irreversible cell cycle arrest. Therefore, the ability of virus-infected cells to circumvent the senescence program is essential for the long-term survival and proliferation of infected cells and the likelihood of transformation. We review the multiple strategies used by human DNA and RNA tumor viruses to subvert telomerase functions during cellular transformation and carcinogenesis. Epstein-Barr virus, Kaposi sarcoma-associated herpesvirus, human papillomavirus, hepatitis B virus, hepatitis C virus, and human T-cell leukemia virus-1 each can increase transcription of the telomerase reverse transcriptase. Several viruses appear to mediate cis-activation or enhance epigenetic activation of telomerase transcription. Epstein-Barr virus and human papillomavirus have each developed posttranscriptional mechanisms to regulate the telomerase protein. Finally, some tumor virus proteins can also negatively regulate telomerase transcription or activity. It is likely that, as future studies further expose the strategies used by viruses to deregulate telomerase activity and control of telomere length, novel mechanisms will emerge and underscore the importance of increased telomerase activity in sustaining virus-infected cells and its potential in therapeutic targeting.

PMID:
18182620
[PubMed - indexed for MEDLINE]
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