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Journal of Virology, May 2003, p. 5985-5996, Vol. 77, No. 10
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.10.5985-5996.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

The RNA Subunit of Telomerase Is Encoded by Marek's Disease Virus

Laëtitia Fragnet,1 Maria A. Blasco,2 Wolfram Klapper,3 and Denis Rasschaert1*

Laboratoire de Virologie et Barrière d'Espèce, INRA, Centre de Recherches de Tours, Unité de Recherche 086, 37380 Nouzilly, France,1 Department of Immunology and Oncology, Centro Nacional de Biotecnologia-CSIC, Campus Cantoblanco, E-28049 Madrid, Spain,2 Institute for Hematopathology, Center for Pathology and Applied Cancer Research, Universität Kiel, Niemannsweg 11, D-24105 Kiel, Germany3

Received 18 December 2002/ Accepted 14 February 2003

Marek's disease virus (MDV) is a herpesvirus of chickens that induces T lymphomas and tumors within 4 to 5 weeks of infection. Although the ability of MDV to induce tumors was demonstrated many years ago and although a number of viral oncogenic proteins have been identified, the mechanism by which the MDV is implicated in tumorigenesis is still unknown. We report the identification of a virus-encoded RNA telomerase subunit (vTR) within the genome of MDV. This gene is found in the genomic DNA of the oncogenic MDV strains, whereas it is not carried by the nononcogenic MDV strains. The vTR sequence exhibits 88% sequence identity with the chicken gene (cTR). Our functional analysis suggests that this telomerase RNA can reconstitute telomerase activity in a heterologous system (the knockout murine TR-/- cell line) by interacting with the telomerase protein component encoded by the host cell. We have also demonstrated that the vTR promoter region is efficient whatever the species of cell line considered and that vTR is expressed in vivo in peripheral blood leukocytes from chickens infected with the oncogenic MDV-RB1B and the vaccine MDV-Rispens strains. The functionality of the vTR gene and the potential implication of vTR in the oncogenesis induced by MDV is discussed.

* Corresponding author. Mailing address: Laboratoire de Virologie et Barrière d'Espèce, UR086, INRA, Centre de Recherches de Tours, 37380 Nouzilly, France. Phone: (33) 02-47-42-79-42. Fax: (33) 02-47-42-77-74. E-mail: rasschae{at}tours.inra.fr.

Journal of Virology, May 2003, p. 5985-5996, Vol. 77, No. 10
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.10.5985-5996.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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