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New fossil virus found in human genome

11 January 2010
Appeared in BioNews 540

Around 8 per cent of human DNA is known to have come from so-called 'retroviruses' - a virus type that includes HIV (human immunodeficiency virus). This week, the journal Nature reported that scientists have discovered a second group of viruses - 'bornaviruses' - can also be passed between generations in our DNA. This makes them a previously unknown source of human DNA mutation and innovation. What's more, the fossil viruses have been co-opted to manufacture proteins.

Borna disease virus (BDV), an RNA virus first discovered in horses, infects host neurons and carries out its entire lifecycle in their nucleus. The scientists, led by Keizo Tomonaga of Osaka University, discovered a fossil record of past BDV infections in primate DNA going back 40 million years. BDV infections were also found in other mammals. In squirrels, the first recorded infection was less than 10 million years ago. This is the first evidence that non retroviruses can permanently 'fix' themselves into mammal DNA.

Some of the bornavirus-derived DNA generates human proteins, the researchers found, although it is unclear whether these serve any function. Among the many sections of Borna-like genetic sequences they discovered, two were annotated as protein-coding sequences. One of these is known to interact with well-known cell proteins, showing it had been co-opted as a mammal gene

Bornaviruses enter human DNA using a different mechanism than retroviruses. Bornaviruses don't need to write their RNA into the host cell's DNA to replicate, unlike retroviruses. Retroviruses as passed from parent to offspring when they use the enzyme reverse transcriptase to transcribe themselves onto chromosomes in a host's egg or sperm cell.

The researchers believe that L1 long interspersed nucleotide elements (LINEs) are responsible for transcribing bornavirus RNA into mammal DNA. LINEs - pieces of mobile DNA that copy and reinsert themselves into mammal genomes - have been ubiquitous in mammal cells for more than 100 million years, according to Nature. In addition to transcribing their own RNA, they can also act on other RNA, including, perhaps, from bornaviruses.

The researchers could find BDV DNA in infected mice after just 30 days, suggesting that BDV readily inserts itself into the mouse genome and may be a new source of mutation in neurons.

But, although BDV has been linked to schizophrenia, Professor Tomonaga told Wired magazine his findings were 'not likely' to be the mechanism. Because bornavirus genes are randomly inserted by LINEs: 'it is not conceivable that mutations [caused] by the integration lead to the specific brain disorders, such as schizophrenia', he said.

Endogenous non-retroviral RNA virus elements in mammalian genomes
Nature |  7 January 2010
Human Genome Is Part Bornavirus
Wired |  7 January 2010
Virology: Bornavirus enters the genome
Nature |  7 January 2010
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