VIRAL stowaways hidden in the DNA of mammals could be more than just idle passengers – they could be crucial for fetal development.
Endogenous retroviruses (ERVs) typically account for 8 to 10 per cent of mammalian DNA, including our own, but until recently were thought to be relics of infection dumped in the genetic equivalent of the attic.
Lab studies had suggested that the endogenous Jaagsiekte sheep retrovirus (enJSRV) might help the early embryo implant in the uterus and transform it from a clump of cells into a shape from which the placenta can develop.
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To test this notion in live animals, Tom Spencer and his colleagues at Texas A&M University in College Station, injected the uterine linings of ewes with a drug that blocks the activity of enJSRV. Pregnant sheep given the virus-blockers miscarried (Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.0603836103).
Spencer believes that enJSRV probably incorporated itself into the genome of some sheep by chance following an infection, and that it may then have shaped the evolution of the placenta by producing a protein that was better at orchestrating the early stages of fetal development than the sheep’s own protein. Eventually, the enJSRV became part of every sheep’s inheritable DNA, he says.
EnJSRV has a human counterpart called HERV-W, which is thought to play a similar role in embryonic development. By finding out more about how enJSRVs function in development of the sheep placenta, Spencer’s team hopes to throw light on how defects in the process might trigger miscarriages in women.
Robin Weiss, who studies ERVs at University College London, points out the usefulness of the sheep studies, because you can’t switch off expression of the HERV-W gene in women to see if it triggers miscarriage. “So this is an animal study showing what we’ve kind of known about in humans.”
“The viral stowaway was better at orchestrating the early stages of fetal development than the sheep’s own protein”
Manipulating ERVs could also yield new ways of treating viral infections, since ERVs are also known to protect against infection with certain viruses. In sheep, for example, enJSRVs block the life cycle of related but infectious JSRVs which cause lung cancers and pneumonia, and which killed Dolly the cloned sheep. None of the retroviruses “adopted” by the human genome has any surviving infectious counterpart, suggesting that our adopted viruses have “won” the battle for us and wiped out viruses that were previously infectious, says Spencer.
The tantalising implication is that in the future, today’s viruses will be adopted by our DNA and help protect us from killers such as HIV and hepatitis B.
