Borna Virus: Hunting Fossil Viruses in Human DNA

The borna virus is at once, obscure and grotesque. It can infect mammals and birds, but scientists know little about its effects on its victims.

In some species it seems to be harmless, but it can drive horses into wild fits. The horses sometimes kill themselves by smashing in their skulls.

In other cases, they starve themselves to death. Some scientists have even claimed that borna viruses alter human behavior, playing a role in schizophrenia and bipolar disorder, although others say there is no solid evidence of a link.

The virus now turns out to have an intimate bond with every person on Earth. In the latest issue of Nature, a team of Japanese and American scientists report that the human genome contains borna virus genes. The virus infected our monkey-like ancestors 40 million years ago, and its genes have been passed down ever since.

Borna viruses are not the only viruses lurking in our genome. Scientists have found about 100,000 elements of human DNA that probably came from viruses. But the borna virus belongs to a kind of virus that has never been found in the human genome before. Its discovery raises the possibility that many more viruses are left to be found.

Scientists who hunt for these viruses think of themselves as paleontologists searching for fossils. Just as animals get buried in rock, these viruses become trapped in the genomes of their hosts. While their free-living relatives continue to evolve, fossil viruses are effectively frozen in time.

“We can really dig fossils out of the genome and literally put them back together,” said Cédric Feschotte, a genome biologist at the University of Texas, Arlington. “It’s like putting a hominid back together and asking it if it can walk upright.”

When scientists sequenced the human genome in 2001, they noticed many segments that bore a striking resemblance to genes in retroviruses, a class of viruses that includes H.I.V.

Retroviruses carry their genetic material in a single-stranded version of DNA, called RNA. To make new viruses, they make DNA versions of their genes, which are inserted into a host cell’s genome. The cell then reads the retrovirus’s genes as if they were its own, and manufactures new retroviruses.

Scientists speculated that every now and then a retrovirus inserted itself into a host cell and then failed to turn it into a virus factory. If the trapped retrovirus happened to be in sperm or egg cells, its DNA might be passed down to the host’s descendants. From generation to generation, the virus’s DNA would mutate. It would lose its ability to produce normal viruses. For a while it might be able to make new viruses that could re-infect the same cell, but over enough time, the viruses would become disabled.

In recent years, scientists have found several lines of evidence to support this idea. . Koala retroviruses, for example, appear to be in the middle of the journey. The viruses can move from one koala to another. But in some populations of koalas, the virus’s DNA is permanently lodged in their genomes.

Thierry Heidmann of the Gustave Roussy Institute in France and his colleagues put the fossil virus hypothesis to a spectacular test: they tried to resurrect a dead retrovirus. They first identified a number of copies of the same virus-like stretch of DNA in the human genome. Each version had its own set of mutations that it acquired after the virus had invaded our ancestors.

By comparing the copies, Dr. Heidmann and his colleagues were able to figure out what the original sequence of the virus’s genes had been. When they synthesized the genes from scratch and injected the genetic material into cells, the cells produced new viruses.

“It was a tour-de-force of an experiment,” said John Coffin, an expert on fossil viruses at Tufts University.

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