Study Finds Surprising Benefit of Viral DNA: Fighting Other Viruses

[Guest Nicole]

What could be more alien than a virus? It’s a nanobiological weapon — a microscopic protein shell holding a few genes that hijack a cell’s internal machinery, forcing it to make new viruses. The battles we fight with these alien enemies brings malaise, scars and even death.

Yet as foreign as viruses may seem, the boundary between us and them is turning out to be remarkably blurry. We use DNA from viruses to do things that are essential to our own survival, scientists are finding. Somehow, we have managed to domesticate some of these invaders.

A number of viruses replicate by inserting their DNA into our own genes. On rare occasions, their genes get passed down to future generations.

At first, the newly acquired genes behave a lot like regular virus genes. They can still coax host cells to make full-fledged viruses that can escape and infect other victims.

But over the generations, they lose the ability to escape human cells. They can still make copies of themselves, but those copies get incorporated into the host cell’s DNA. Over time these so-called endogenous retroviruses lose even the ability to replicate, becoming harmless fragments adrift in the human genome.

Endogenous retroviruses first invaded the cells of our primate ancestors more than 50 million years ago. Scientists have identified over 100,000 of these fragments in the human genome, accounting for 8 percent of our DNA.

Some of these fragments have become part of our biology and perform tasks that benefit us. “A host essentially takes over a viral gene and puts it to work for its own ends,” said Aris Katzourakis, an evolutionary biologist at the University of Oxford.

Human cells may have even co-opted viral DNA for a particularly ironic purpose: to fight other viruses.

Twenty years ago, British scientists investigated a virus-fighting protein called Fv1. It protects mice by latching onto invading viruses and preventing them from inserting their DNA into the genome of a mouse cell. The gene that encodes Fv1 came originally from a mouse-infecting virus, the researchers discovered.

Other proteins produced by viral DNA block the receptors through which newcomer viruses invade. Some viral proteins disrupt the replication of attacking viruses, leaving them unable to invade other cells.

On Thursday in the journal Science, scientists reported that human ancestors also harnessed viral DNA to rewire their own genetic circuitry.

Guillaume Bourque, a geneticist at McGill University who was not involved in the study, praised it for revealing a new way in which evolution harnessed viral DNA to strengthen the immune system. “In that sense, it’s a first,” he said.

To fight invading viruses, a cell needs to turn on many genes at once. The genetic switches that make this possible are stretches of DNA next to each gene, which are themselves activated by proteins.

From left, University of Utah geneticists Cedric Feschotte, Edward Chuong and Nels Elde. Their research suggests that viral DNA fragments in the human genome may help fight viral infections.

UNIVERSITY OF UTAH HEALTH SCIENCES

One such protein is interferon, which is produced when a cell is attacked by a virus. Interferon turns on genes that cells use to defend themselves.

Cedric Feschotte and his colleagues at the University of Utah wondered if our cells harnessed viral gene switches to turn on immune genes. They discovered many pieces of viral DNA sitting next to genes that belong to the interferon network.

The scientists edited the DNA of human cells they grew in a dish, chopping out some of the viral switches near interferon-responsive genes. Then they exposed those cells to interferon. The immunity genes, they found, barely woke up.

In another experiment, the team exposed the altered cells to viruses and found that the cells mounted only a weak defense. “They became more susceptible to infection,” Dr. Feschotte said.

The results suggest that many of the gene switches that help defend our cells from viruses actually came from viruses.

Dr. Feschotte noted that a number of viruses that infect humans today have gene switches that turn on their genes when they sense their host cells have launched an interferon defense. Such gene switches would have been easily captured by our own cells.

The new study adds even more evidence of the importance of viral DNA in our evolution. By spreading their DNA around our genome, viruses provided us with new switches that our cells could harness.

But understanding the full effect of viruses on our evolution will take years, according to Dr. Feschotte. “It’s the sort of thing that I think about night and day,” he said.

Source: http://mobile.nytimes.com/2016/03/03/science/study-finds-surprising-benefit-of-viral-dna-fighting-other-viruses.html