Anendogenous viral element (EVE) is aDNA sequence derived from avirus, and present within thegermline of anon-viral organism. EVEs may be entire viral genomes (proviruses), or fragments of viral genomes. They arise when a viral DNA sequence becomes integrated into thegenome of agerm cell that goes on to produce a viable organism. The newly established EVE can beinherited from one generation to the next as anallele in the host species, and may even reachfixation.
Endogenous retroviruses and other EVEs that occur as proviruses can potentially remain capable of producinginfectious virus in their endogenous state. Replication of such 'active' endogenous viruses can lead to the proliferation of viral insertions in the germline. For most non-retroviral viruses, germline integration appears to be a rare, anomalous event, and the resulting EVEs are often only fragments of the parent virus genome. Such fragments are usually not capable of producing infectious virus, but may expressprotein orRNA and evencell surface receptors.
EVEs have been identified inanimals,plants andfungi.[1][2][3][4] Invertebrates EVEs derived fromretroviruses (endogenous retroviruses) are relatively common. Because retroviruses integrate into thenuclear genome of thehost cell as an inherent part of theirreplication cycle, they are predisposed to enter the host germline. In addition, EVEs related toparvoviruses,filoviruses,bornaviruses andcircoviruses have been identified in vertebrate genomes. In plant genomes, EVEs derived frompararetroviruses are relatively common. EVEs derived from other, non-retrotranscribing virus families, such asGeminiviridae, have also been identified in plants. Moreover, EVEs related togiant viruses (aka GEVEs) ofphylumNucleocytoviricota (NCLDV) similar toAureococcus anophagefferens virus (AaV) have been found in 2019/2020.[5]
EVEs are traditionally identified by similarity to known viruses. In 2021, it has been demonstrated that thek-mer composition of endogenous RNA virus resemble that of their exogenous counterparts. As a result, it is now possible to identify novel groups of endogenous RNA viruses whose exogenous relatives have become extinct.[6]
EVEs are a rare source of retrospective information about ancient viruses. Many are derived from germline integration events that occurred millions of years ago, and can be viewed as viralfossils. Such ancient EVEs are an important component ofpaleovirological studies that address the long-termevolution of viruses.Identification oforthologous EVE insertions enables the calibration of long-term evolutionary timelines for viruses, based on the estimated time sincedivergence of the ortholog-containing host species groups. This approach has provided minimum ages ranging from 30 to 93 million years for theParvoviridae,Filoviridae,Bornaviridae andCircoviridae families of viruses,[3] >100 million years in theFlaviviridae,[7] and 12 million years for theLentivirus genus of theRetroviridae family. EVEs also facilitate the use ofmolecular clock-based approaches to obtain calibrations of viral evolution indeep time.[8][9]
EVEs can sometimes provide aselective advantage to the individuals in which they are inserted. For example, some protect against infection with related viruses.[10][11] In some mammal groups, includinghigher primates, retroviralenvelope proteins have beenexapted to produce a protein that is expressed in theplacentalsyncytiotrophoblast, and is involved in fusion of thecytotrophoblast cells to form thesyncytial layer of the placenta. In humans this protein is calledsyncytin, and is encoded by anendogenous retrovirus called (ERVWE1) onchromosome seven. Remarkably, the capture of syncytin or syncytin-like genes has occurred independently, from different groups of endogenous retroviruses, in diverse mammalianlineages. Distinct, syncytin-like genes have been identified inprimates,rodents,lagomorphs,carnivores, andungulates, with integration dates ranging from 10 to 85 million years ago.[12]