Filoviruses are ancient and integrated into mammalian genomes

Abstract

BackgroundHemorrhagic diseases from Ebolavirus and Marburgvirus (Filoviridae) infections can be dangerous to humans because of high fatality rates and a lack of effective treatments or vaccine. Although there is evidence that wild mammals are infected by filoviruses, the biology of host-filovirus systems is notoriously poorly understood. Specifically, identifying potential reservoir species with the expected long-term coevolutionary history of filovirus infections has been intractable. Integrated elements of filoviruses could indicate a coevolutionary history with a mammalian reservoir, but integration of nonretroviral RNA viruses is thought to be nonexistent or rare for mammalian viruses (such as filoviruses) that lack reverse transcriptase and replication inside the nucleus. Here, we provide direct evidence of integrated filovirus-like elements in mammalian genomes by sequencing across host-virus gene boundaries and carrying out phylogenetic analyses. Further we test for an association between candidate reservoir status and the integration of filoviral elements and assess the previous age estimate for filoviruses of less than 10,000 years.ResultsPhylogenetic 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.ConclusionsOur 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).

Molecular Evolution of Viruses of the Family Filoviridae Based on 97 Whole-Genome Sequences

“…5), which is about the time the Earth emerged from the last ice age. Our estimate is similar to a previous calculation (7,100 to 7,900 years) based on synonymous and nonsynonymous substitution ratios (25) and far younger than other recent assessments using non-clock-based methods that rely on the assumption of filovirus-like elements that appear to have been integrated into the genome of a variety of mammals and subjected to different evolutionary pressures (27,28). Additional approximations of MRCA that resulted in older estimates than those generated in this study differed in terms of more-limited numbers of whole-genome taxa as well as methodology (4,26).…”

“…Although the filoviruses are thought to have originated quite some time ago, age estimates have ranged from a few thousand (25,26) to hundreds of thousands (4) to a few million (27,28) years ago. Further confusing the issue, some authors have presented data indicating that viruses of at least one filovirus species (Zaire ebolavirus) share a most recent common ancestor (MRCA) in the very recent past (29)(30)(31)(32).…”

Analysis of Ebolavirus with Decision Tree and Apriori algorithm

“…After analysis using Decision Tree, trying 9, 13, and 17 windows of analysis, we thoroughly investigated genetic structure of Bundibugyo Ebolavirus, Reston Ebolavirus, Sudan Ebolavirus, TaiForest Ebolavirus, and Zaire Ebolavirus. [15] As a result of analysis, we found that high windows shows more detailed information about DNA sequences of Ebolaviruses and there are similarities of DNA sequences between the species of it. Since Reston Ebolavirus does not cause vital disease to humans as it does to animals such as pigs and monkeys, we look forward to finding the ways of curing Ebolavirus disease [16].…”

Endogenous hepadnaviruses, bornaviruses and circoviruses in snakes

“…For example, EVE discovery can expand the past and current known host range of viral families [7][8][9], contribute to the characterization of the viral flora infecting a specific organism or lineage [10,11] and help to identify reservoir species and/or reconstruct complex transmission routes of zoonotic viruses [12][13][14]. Furthermore, endogenization events can be dated and used to calibrate long-term evolutionary patterns of modern virus families [15][16][17][18].…”