The Journal of Experimental Medicine
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Published online 1 May 2006 doi:10.1084/jem.20052240
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 203, Number 5, 1307-1317
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ARTICLE

 A virus-encoded telomerase RNA promotes malignant T cell lymphomagenesis

Sascha Trapp1, Mark S. Parcells2, Jeremy P. Kamil1, Daniel Schumacher1, B. Karsten Tischer1, Pankaj M. Kumar2, Venugopal K. Nair3, and Nikolaus Osterrieder1

1 Department of Microbiology and Immunology, Cornell University, Ithaca, NY 14853
2 Department of Animal and Food Science, University of Delaware, Newark, DE 19717
3 Institute for Animal Health, Compton, Berkshire RG20 7NN, UK

CORRESPONDENCE Nikolaus Osterrieder: no34{at}cornell.edu.

Telomerase is a ribonucleoprotein complex consisting of two essential core components: a reverse transcriptase and an RNA subunit (telomerase RNA [TR]). Dysregulation of telomerase has been associated with cell immortalization and oncogenesis. Marek's disease herpesvirus (MDV) induces a malignant T cell lymphoma in chickens and harbors in its genome two identical copies of a viral TR (vTR) with 88% sequence identity to chicken TR. MDV mutants lacking both copies of vTR were significantly impaired in their ability to induce T cell lymphomas, although lytic replication in vivo was unaffected. Tumor incidences were reduced by >60% in chickens infected with vTR– viruses compared with animals inoculated with MDV harboring at least one intact copy of vTR. Lymphomas in animals infected with the vTR– viruses were also significantly smaller in size and less disseminated. Constitutive expression of vTR in the chicken fibroblast cell line DF-1 resulted in a phenotype consistent with transformation as indicated by morphological alteration, enhanced anchorage-independent cell growth, cell growth beyond saturation density, and increased expression levels of integrin {alpha}v. We concluded that vTR plays a critical role in MDV-induced T cell lymphomagenesis. Furthermore, our results provide the first description of tumor-promoting effects of TR in a natural virus–host infection model.

Abbreviations used: BAC, bacterial artificial chromosome; CEC, chicken embryo cell; chTR, chicken telomerase RNA; CR, conserved region; iNOS, inducible nitric oxide synthetase; MD, Marek's disease; MDV, MD virus; qPCR, quantitative real-time PCR; TERT, telomerase reverse transcriptase; TR, telomerase RNA; vTR, viral TR.

J.P. Kamil's present address is Dept. of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115.

B.K. Tischer's present address is Institut für Infektionsmedizin, Christian-Albrechts-Universität, 24159 Kiel, Germany.


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