circovirus

During the replication of retroviruses, a double-stranded DNA copy of the viral RNA genome is synthesized by reverse transcription and integrated into the genomes of the infected cell. When retroviral DNA is integrated into the DNA of germ line cells, it is passed on to future generations in Mendelian fashion as an endogenous provirus. Until very recently, retroviruses were the only known endogenous viruses. This honor has now been extended to other RNA viruses, and to circoviruses and parvoviruses, which possess single-stranded DNA genomes. Such integration events constitute a fossil record from which it is possible to determine the age of viruses.

The first non-retroviral endogenous virus described was bornavirus, a virus with a negative-stranded RNA genome. Bornaviral sequences were found in the genomes of humans, non-human primates, rodents, and elephants. Phylogenetic analyses revealed that these sequences entered the primate genome over 40 million years ago. Endogenous filovirus (ebolavirus, marburgvirus) sequences were subsequently identified in the genomes of bats, rodents, shrews, tenrecs and marsupials. Based on these analyses it was estimated that filoviruses are at least tens of millions of years old. The presence of endogenous bornavirus and filovirus sequences were subsequently confirmed and extended to 19 different vertebrate species. Endogenous hepadnaviruses probably entered the genome of the zebra finch 19 million years ago.

Recent additions to the endogenous virus catalog are the circoviruses and parvoviruses. The genome of circoviruses are composed of single-stranded DNA, while those of parvoviruses are linear single-stranded DNAs with base-paired ends (figure). Phylogenetic analyses of these endogenous viral sequences reveal that both virus families are 40 to 50 million years old. Examination of insect genomes has revealed endogenous viral sequences from members of the Bunyaviridae, Rhabdoviridae, Orthomyxoviridae, Reoviridae, and Flaviviridae.

With the exception of retroviruses, these endogenous viral sequences have no role in viral replication – they are accidentally integrated into host DNA. Such sequences are highly mutated and typically comprise only fragments of the viral genome, and therefore cannot give rise to infectious virus. Whether these sequences confer any biological advantage to the host is an interesting question. It is possible that some of the endogenous viral sequences are copied into RNA, or translated into protein, and could have consequences for the host. For example, it has been suggested that synthesis of the bornaviral N protein from endogenous sequences might render the host resistant to infection with bornaviruses.

How are non-retroviral genomes integrated into the host DNA? For viruses with an RNA genome, the nucleic acid must enter the nucleus (perhaps accidentally for viruses without a nuclear phase) and be converted to a DNA copy by reverse transcriptase encoded by endogenous retroviruses. Hepadnaviruses encode a reverse transcriptase which produces the genomic DNA from an RNA template. In all cases, recombination could lead to integration of viral DNA into the host chromosome.

Almost half of the human genome is made up of mobile genetic elements, which includes endogenous proviruses and other sequences derived from retroviruses such as retrotransposons, retroposons, and processed pseudogenes. It seems likely that even more diverse viral sequences lurk in cellular genomes, awaiting discovery.

Horie M, Honda T, Suzuki Y, Kobayashi Y, Daito T, Oshida T, Ikuta K, Jern P, Gojobori T, Coffin JM, & Tomonaga K (2010). Endogenous non-retroviral RNA virus elements in mammalian genomes. Nature, 463 (7277), 84-7 PMID: 20054395

Taylor DJ, Leach RW, & Bruenn J (2010). Filoviruses are ancient and integrated into mammalian genomes. BMC evolutionary biology, 10 PMID: 20569424

Belyi VA, Levine AJ, & Skalka AM (2010). Unexpected inheritance: multiple integrations of ancient bornavirus and ebolavirus/marburgvirus sequences in vertebrate genomes. PLoS pathogens, 6 (7) PMID: 20686665

Gilbert C, & Feschotte C (2010). Genomic fossils calibrate the long-term evolution of hepadnaviruses. PLoS biology, 8 (9) PMID: 20927357

Katzourakis A, & Gifford RJ (2010). Endogenous viral elements in animal genomes. PLoS genetics, 6 (11) PMID: 21124940

Belyi VA, Levine AJ, & Skalka AM (2010). Sequences from ancestral single-stranded DNA viruses in vertebrate genomes: the parvoviridae and circoviridae are more than 40 to 50 million years old. Journal of virology, 84 (23), 12458-62 PMID: 20861255