Phoenix - reborn from junk DNA
Thierry Heidmann's team at the Institut Gustave Roussy in Villejuif near Paris brought back a viral fossil that infected our ancestors millions of years ago. Once again this raised fears of a pandemic straight out of the Petri dish. But "Phoenix" is far from being a killer. Brynja Adam-Radmanic took a closer look.
Only last year scientists recovered the deadly Spanish flu agent from lung tissue of corpses frozen in Alaskan permafrost since 1918. To find Phoenix, Dewannieux and his collegues didn't have to exhume anybody. The fragments from which they pieced the virus together are rather well-known residents in all of us - albeit in their non-functional form as human endogenous retroviruses (HERVs) lingering in our genomes.
Ancient retroviruses infected germ line cells of our primate ancestors and became crippled by mutations after their insertion. Sequences of viruses, which are no longer actively transmitted between individuals, are conserved in our genome and passed down the generations in Mendelian fashion.
Phoenix, however, is the first evidence that HERVs can be turned into infectious viruses again. The research group led by Heidmann was able to identify mutations in the HERV-K-family by assembling a consensus sequence of dozens of HERV-K members. They converted this information into a viral genome and showed that human cell lines produce viral particles of Phoenix, though they are of extremely low infectivity.
Hence, Phoenix is far from being the flesh-eating monster the flu virus H1N1 was at the end of World War I, presumably because human cells have become resistant against retroviruses of the Phoenix type. The reasons for bringing the two viruses back into existence were quite different. The flu virus was resurrected specifically due to its capacity as an infectious agent and potential to kill millions of people. Researchers wanted to know what made it so dangerous.
Phoenix, however, wasn't brought back to determine how infectious it is for people. To the contrary, Thierry Heidmann's team studies retroviral sequences in the human genome with a view to their putative roles in oncogenesis. HERVs are suspected of contributing to cancer in different ways. Firstly, as mobile elements, HERVs possess the nasty aptitude of spawning by way of a "copy and paste" mechanism and, subsequently, introducing mutations. As Heidmann's lab could show, Phoenix is not one of these retrotransposons but instead amplifies via an extra-cellular pathway involving re-infection.
Furthermore, HERVs sometimes express retroviral envelope genes with immunosuppressive functions; a suspicious property in which Heidmann's lab takes special interest. They also used the envelope genes to complete the identification of the human endogenous retroviruses, to classify them and establish their phylogeny as well as that of other infectious viruses. Hence, trying to rebuild a progenitor of one of them seems to be just another step.
Another revelation was that, although Phoenix needed a little help from DNA technology to be brought back into existence, the work of the scientists shows that Phoenix could well rise from the ashes all by itself, just like the mythical bird after which it was named. They show "that in vitro recombinations among present-day HERV-K loci can similarly generate functional HERV-K elements, indicating that human cells still have the potential to produce infectious retroviruses."
Dewannieux M, Harper F, Richaud A, Letzelter C, Ribet D, Pierron G, Heidmann T. Identification of an infectious progenitor for the multiple-copy HERV-K human endogenous retro elements. Genome Res. 2006 Oct 31 (Epub ahead of print):
http://dx.doi.org/10.1101/gr.5565706
Endogenous retroviruses and oncogenesis in a brochure on the IGR website (don't miss Heidmann's smiling amidst fancy bubbles in 70s retro design with molecular models flying around his head...):
http://www.igr.fr/brochure_recherche/eng/retroviral-sequence-3.shtml
