A French team has managed to resuscitate a 5-million-year-old retrovirus from the group of human endogenous retroviruses (HERVs), rendering able to produce infections. This retrovirus is named Phoenix and is a primitive form in a large virus family, many being linked to cancer.
This is the first research to generate an infectious retrovirus from a mobile element in the human genome, which is a breakthrough in the field of retrovirus science. "Phoenix became frozen in time after it integrated into the human genome about 5 million years ago," explains Dr. Thierry Heidmann.
"In our study, we've recovered
this ancestral state and shown that it has the potential for infectivity."
Retroviruses have RNA genomes and make the host to create DNA "copies" of their RNA, which are incorporated into the host's genome. These process have been occurring from millions of years ago inside the human genome, and the viral-originated DNA sequences passed on from generation to generation.
They comprise nearly 8% of the human genome, but most were inactivated long ago by mutations. The team reactivated the HERV-K(HML2) family, Phoenix's, an evolutionarily "young" family inside the retroviruses' group.
HERV-K(HML2) elements, determined their consensus sequence, and then constructed a retrovirus-Phoenix was achieved by mutating 30 ancient HERV-K(HML2) elements from the human genome, using as backbone DNA from 2 living HERVs.
Phoenix particles proved to be able to infect mammalian cells in culture. Infectivity level was very low, 1000 times weaker than HIV, because mammals have evolved mechanisms to control retrovirus propagation. "Phoenix has produced some 'genomic offspring' that may be responsible for the synthesis of the retroviral particles that can be observed in some human cancers such as germline tumors and melanomas," says Heidmann.
"This work will be helpful in tracking down the role of retroviruses in these human diseases."
"It's a Jurassic Park kind of experiment to resurrect an old virus," says John Coffin who studies retroviruses at Tufts University in Boston, Massachusetts. "It's just kind of cool."
Image courtesy: Russell Kightley
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