Filoviruses are ancient and integrated into mammalian genomes

Phylogenetic and sequencing evidence from gene boundaries was consistent with integration of filoviruses in mammalian genomes. We detected integrated filovirus-like elements in the genomes of bats, rodents, shrews, tenrecs and marsupials. Moreover, some filovirus-like elements were transcribed and the detected mammalian elements were homologous to a fragment of the filovirus genome whose expression is known to interfere with the assembly of Ebolavirus. The phylogenetic evidence strongly indicated that the direction of transfer was from virus to mammal. Eutherians other than bats, rodents, and insectivores (i.e., the candidate reservoir taxa for filoviruses) were significantly underrepresented in the taxa with detected integrated filovirus-like elements. The existence of orthologous filovirus-like elements shared among mammalian genera whose divergence dates have been estimated suggests that filoviruses are at least tens of millions of years old.Our findings indicate that filovirus infections have been recorded as paleoviral elements in the genomes of small mammals despite extranuclear replication and a requirement for cooption of reverse transcriptase. Our results show that the mammal-filovirus association is ancient and has resulted in candidates for functional gene products (RNA or protein).The ongoing threat of emerging hemorrhagic diseases has made the search for reservoir species with a history of coevolution with filoviruses a priority [1,2]. Outbreaks of filovirus infections are known from Africa and the Phillipines [3-5] and, in some cases, the mortality of primates is so severe as to raise concerns of extinction [5]. Bats are considered a candidate for a reservoir based on the detection of filovirus-specific RNA, antibodies, and viral particles [1,6-10]. Still, the average seroprevalence in tested bats is much smaller than expected (usually < 5%) for large colonies of a main reservoir [6], and the ability of bats to maintain a persistent hypovirulent infect