Viral fossil brought back to life

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 study that creates new
viruses or activates old ones 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.

http://sciencenow.sciencemag.org/cgi/content/full/2006/1101/4

/Siyavash
2006-11-02 09:32
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