In a controversial study, researchers have resurrected a retrovirus that infected our ancestors millions of years ago and now sits frozen in the human genome. Published online by Genome Research this week, the study may shed new light on the history of these genomic intruders, as well as their role in tumors. Although this particular virus, dubbed Phoenix, is a wimpy one, some argue that resuscitating any ancient virus is inherently risky and that the study should have undergone stricter reviews.
Retroviruses have the ability to make DNA copies of their RNA genomes and incorporate these into the host's genome. If this happens in a germ cell, the copy can be passed on to future generations. Indeed, the human genome is littered with the remnants of such human endogenous retroviruses (HERVs) (ScienceNOW, 29 September 2004). So far, researchers had been unable to recover a complete, functional HERV from a human genome however; part of the reason, they assumed, was that mutations accumulated over the millennia had rendered such viruses dysfunctional.
A team led by Thierry Heidmann at the Institut Gustave Roussy in Villejuif, France, near Paris, decided to try to awaken the ancestor of an entire family of HERVs called HERV-K(HML2). To "correct" for mutations, the researchers took dozens of known HERV-K(HML2) sequences and aligned them to create a so-called "consensus" sequence. Then they converted this information into a complete viral genome.
The researchers showed that the newly crated virus could infect a variety of human cell lines and replicate. But its infectivity was extremely low, perhaps because human cells have evolved resistance against such viral invaders.
"I think it's pretty exciting," says John Coffin, who studies retroviruses at Tufts University in Boston. Phoenix may shed new light on how HERVs became part of the human genome and what role they play there, he says; it may also be a tool to study endogenous retroviruses' alleged role in tumor progression.
Others worry that the study sets a dangerous precedent. Although it was approved by the French research ministry's Genetic Engineering Committee, Richard Ebright, a molecular biologist at Rutgers University in New Jersey, says any work involving the potential reconstruction of an extinct or eradicated infectious agent should be subject to a special review at the national or international level. What's more, he says, because the researchers couldn't be absolutely sure about Phoenix's infectivity, the study should have been carried out under Biosafety level 4 conditions--the best-protected labs available--instead of the level 3 conditions utilized.
In the field, the wisdom of reviving endogenous retroviruses has long been debated, says Johannes Löwer, president of the Paul Ehrlich Institute in Langen, Germany, who decided against the idea himself. But Heidmann contends the risks in his study were extremely low. The virus was genetically modified in such a way that it could replicate only once, he explains, and a previous study had suggested it would have weak infectivity.