Abstract
Papillomaviruses (PVs) are small DNA viruses that infect the skin and mucosal membranes of many vertebrates and have been associated with epithelial neoplasia. In humans, over one hundred PV types have been identified to date. Only a limited number have been characterized so far in other mammal species. In bottlenose dolphins (Tursiops truncatus), only 3 PVs have been previously identified. We amplified four complete novel PV genomes (TtPV4, TtPV5, TtPV6 and TtPV7) from biopsy samples of bottlenose dolphin genital papillomatous lesions using rolling circle amplification and degenerate PCR techniques. Analysis of these full-length genomes revealed that they form a monophyletic group with other characterized cetacean PVs. Recently, the association between infection with multiple PV types and increased oncogenic risk in humans has been emphasized.1,2 While infections with up to 14 PV types have been reported in humans3, PV co-infection studies in non-human animal species have not yet been reported. To search for multiple PV infections in bottlenose dolphins, we screened both genital and oral papillomatous lesions and non-lesioned samples (n = 71) by PCR using primers based on the conserved regions of the PV E1 protein. The PCR amplicons were sequenced and compared to dolphin PVs available in the GenBank database. A total of 26 genital and one oral PV genotypes were identified in lesioned and non-lesioned samples. Similar to humans, co-infections of up to nine genital PVs in a single dolphin were detected. This study revealed that bottlenose dolphins represent the first non-human natural model of PV co-infections. Comparative genomics of human and dolphin PVs present a unique opportunity to study the role of PV co-infections in the development of cancer.
Acknowledgements
This work was funded by research grant N° N00014-06-1-0250 from the Office of Naval Research to H.N. and research contract N° N66001-08-D-0070 from the Department of Defense to Dr. Pamela Yochem (Hubbs-SeaWorld Research Institute). The authors would like to thank Dr. P Yochem, and Dr. Stephanie Venn-Watson (U.S. Navy Marine Mammal Program Foundation) for their support on this project, including comments on the abstract and presentation. We would also like to thank Celeste Benham for her assistance in the laboratory.
References
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