A transforming giant virus discovered in Canine Transmissible Venereal Tumour: Stray dogs and Tasmanian devils opening the door to a preventive cancer vaccine

ABSTRACT Background: Canine Transmissible Venereal Tumour (CTVT) along with Tasmanian Devil Facial Tumour and transmissible leukaemia in Mya Arenaria soft shell-clams are the only examples of contagious cancers occurring in nature. In particular, CTVT is the oldest contagious cancer present in the wild world, emerged 11,000 years ago. The attempts to detect a transmissible virus as a causative agent in these form of contagious cancer proved conflicting and the current consensus view is that a transformed cell itself is transmitted and starts the tumor in a new animal, as a parasitic allograft. We modify this perception and report for the first time the isolation of an acutely transforming microbial infectious agent from CTVT. Methods: Giant viral particles were successfully isolated from CTVT specimens through a sucrose gradient, examined at electron microscopy, fully sequenced, used for transformation tests on NIH-3T3 cells and tumorigenic experiments in dogs. Results: The particles isolated from CTVT are giant viral particles with 1.17MB mega-genome. They transformed NIH-3T3 cells in vitro and initiated the typical CTVT lesions in a healthy dog, just one week post-infection. Only the fraction containing the giant viral particles were able to reproduce the tumour, while a filtered supernatant did not. This ruled out the presence of classic filterable viruses. Conclusions: We discovered an infectious microbial agent, acutely transforming in CTVT. The agent shares some of the features that apply to giant Mimiviruses, such as the gigantic size and the presence of a mega-genome. However, distinct from environmental giant Mimiviruses, this mammalian microbial entity has a transforming nature and does not require amoeba co-culture. The biological characteristics depict this large agent halfway in between a classic oncogenic virus and a self-governing microbial cell-like entity. A practical application of this finding could be a new vaccination plan to control the spreading of this contagious cancer among dogs in endemic area as well as a new approach to save the Tasmanian devils that share the same cancer’s tale with stray dogs.