Keen on integration (Image: DR KLAUS BOLLER/SPL)

We may owe our survival and complexity to a stowaway virus that springs to life in the very first cells of human embryos. Not only does the virus seem to protect embryos from other viruses, but it also assists genes when the groundwork is under way for the body plan of a new human.

The finding backs the controversial idea that viruses which took up residence in our DNA millions of years ago may be playing the role of puppet master, quietly influencing our existence and evolution. “We are creatures controlled by viruses,” says Luis Villarreal of the University of California at Irvine.

Retroviruses insert their genetic material into the cells of their human or animal host. At first, this causes disease and death. Over time, however, the host evolves resistance to the virus, allowing any DNA that has embedded itself into sperm or egg cells to be passed down to the next generation. The virus is now known as an endogenous retrovirus or ERV – a permanent fixture in the host’s genome.


Silent protector

About 9 per cent of our genome is thought to have come about this way. Until recently, these viral relics were largely dismissed as inactive “junk” that ceased to have any impact on their host many thousands of years ago. The discovery that HERVK, the most recent ERV to make itself at home in our DNA – probably around 200,000 years ago – is active in human embryos challenges that notion.

Joanna Wysocka and her colleagues at Stanford University in California made the unexpected find while they were analysing gene activity in 3-day-old human embryos, which are bundles of eight cells. Besides DNA from the parents, they found genetic material from HERVK. “The cells were full of viral protein products, some of which had assembled to form viral-like particles,” says Wysocka.

Further experiments revealed that the virus appears to produce a protein that prevents other viruses penetrating the embryo, suggesting it protects the embryo from dangerous circulating viruses, such as influenza. It also seems to play a crucial role in the genetic activity of the embryonic cells, helping to genetic instructions to the cellular protein factories.

Biological dark matter

Tantalisingly, the stowaway virus might even provide clues to what makes us different from chimpanzees and other non-human primates. Some researchers have previously argued that ERVs may play a key role in how species diverge from each other, by activating different body plans and gene networks that may give one individual an edge over other members of the species.

Wysocka’s work backs up this idea, says Patrick Forterre of the Pasteur Institute in Paris. “It shows that the protein products of a relatively ‘recent’ retrovirus integration are present very early on in the embryo, and could be involved in some critical developmental programmes.” The observation that ERVs could also protect the embryo against infection also makes a lot of sense, he says Forterre. “It’s as if retroviruses are competing with each other via their human host.”

Despite being ubiquitous, viruses are often called the dark matter of biology as their influence frequently goes unnoticed. If DNA is a jungle, then the viruses are the animals and plants that live and adapt within it, says Villarreal, who in 2001 showed that the presence of a viral gene is essential for the formation of the human placenta. “DNA is the habitat, and the viruses are the inhabitants,” he says. The most influential viruses are those, like HERVK, that have inserted themselves permanently into our DNA and can be passed on to the next generation.

These viruses have the genetic tools to refashion the hosts’ genes, influencing which are active and when, and with which other genes they interact. This means they have the ability to reshape the physical characteristics of their hosts, says Villarreal. “It’s a massive dynamic pool of colonising genomes.”

Journal reference: Nature, DOI: 10.1038/nature14308