By Ewen Callaway
A retrovirus that has lain dormant in chimpanzees and their ancestors for at least one million years is surrendering its secrets. A team of scientists has resurrected a key portion of the virus and determined how it infects cells.
Ordinarily, endogenous viruses--ancient viruses that were long ago engulfed into their host's genome--are studied on the basis of their DNA sequence alone. Increasingly, however, researchers are bringing such viruses "back to life" and putting them through the same laboratory tests that contemporary viruses are subject to.
"Our major motivation for getting involved in this is to try and explain how our host defences evolved," says Paul Bieniasz, a virologist at the Rockefeller University in New York, whose team identified the molecular receptor that was presumably used by the ancient chimpanzee virus1. Mimicking such defenses could help to combat modern viruses, such as HIV, he says.
Recalled to life
The virus that his team resurrected, known as CERV2, lies within the genomes of contemporary chimpanzees, but not those of humans, suggesting that chimpanzees' ancestors became infected after they diverged from human ancestors 5-6 million years ago. "The virus clearly replicated around the times that nascent humans were trotting around Africa and beginning to think about colonizing the rest of the world," Bieniasz says.
Previously, his team had found that the existence of two human proteins that fend off retroviruses once such viruses have entered cells could not explain why chimpanzee ancestors had been infected but those of humans had not. One protein is ineffective against the chimpanzee virus, whereas the second does not vary enough between humans and chimpanzees to have made a difference, Bieniasz says.
As an alternative, his team proposed that human cells might prevent the chimpanzee viruses from even invading. To test this possibility, Bieniasz's team engineered an unrelated mouse retrovirus coated with the envelope protein that would have allowed the ancient chimpanzee virus to slip into cells. The team expressed different human genes in hamster cells, which were impervious to infection, looking for genes that allowed infection to occur.
The ancient virus exploits a transport protein that normally pipes copper molecules into and out of cells, the authors report in the October 25 issue of Proceedings of the National Academy of Sciences.
However, the copper transporter cannot explain why chimpanzee ancestors were infected with the virus while humans' early relations were spared. Several types of human cell are susceptible to the resurrected virus, and the human version of the copper-transporter protein is identical to that of chimpanzees.
Jonathan Stoye, a virologist at the MRC National Institute for Medical Research in London, says that biological factors aren't needed to explain why only chimpanzee ancestors were infected with the virus. Perhaps, he points out, ancient humans were never exposed to the virus in the first place.
"Chance could have played a big role in this," agrees Bieniasz. "It could be that human ancestors were ecologically isolated from the primate species in which these viruses were replicating." Behavior offers another explanation. "It might be that we didn't bite each other or didn't indulge in some behavior that facilitates transmission of these viruses," he adds.
Despite these open questions, Patric Jern, a virologist at Uppsala University in Sweden, says that the new report points the way for studying viruses fossilized in host genomes, and he expects more and more endogenous viruses to be resurrected and characterized. "These ancient retroviruses have lots to tell," he says.