You are up to 8% virus, at least as far as your genome is concerned. Up to 100,000 pieces of ancient viral DNA live among our genes, yet their function—if any—has long been unclear. A new study suggests that some of this foreign genetic material may boost our immune systems, even protecting us from other viruses.
When a type of virus known as a retrovirus infects a cell, it converts its RNA into DNA, which can then become part of a human chromosome. Once in a while, retroviruses infect sperm and egg cells and become “endogenous,” meaning they are passed down from generation to generation. Endogenous retroviruses, or ERVs, are not able to produce new viruses, and because of that scientists originally assumed that they were harmless genetic fossils.
Controversial studies have long suggested that certain cancers—like some lymphomas—result when ERVs interfere with normal gene function. But more recently, researchers have raised the possibility that these viruses can also be a good thing. ERVs—perhaps inherited millions of years ago—may affect genes important to placenta function and thus may improve our ability to carry a pregnancy. What’s more, there is evidence that they play a role in the early human embryo, where they may help fight off infectious viruses.
In the new study, researchers led by Edward Chuong, a computational biologist at the University of Utah in Salt Lake City, explored whether ERVs help us fend off invaders. They focused on the innate immune system, a first-line of defense. While the adaptive immune system learns to recognize specific invaders and mount responses against them, the innate system is preprogrammed to launch immediate attacks against entire classes of foreigners. The scientists scanned three different human cell lines for ERVs in their DNA that could bind to innate immunity transcription factors, which turn on genes to ramp up the immune system’s attack against pathogens. They found thousands of ERVs.
The researchers predicted that if they removed this viral DNA from the cell, the transcription factors would not function properly, potentially disrupting genes involved in the innate immune response. Using the gene-editing tool CRISPR, they snipped out several endogenous viruses from the cell’s DNA.
When researchers infected these ERV-depleted cells with the vaccinia virus (which may be related to smallpox), they had a much weaker innate immune response than unedited normal cells, the team reports online today in Science. A key immune protein wasn’t produced and thus was not fighting the virus. When researchers later added the genes back into the cells experimentally, immune function was restored.
This new research provides evidence that “an ancient viral element is assisting us against an infection,” Chuong says. He adds that the next step will be to do this experiment in a mouse.
It’s an “elegant study” and “a well-documented example of this fascinating interplay between ERVs and their host organism,” says Dixie Mager, a geneticist at British Columbia Cancer Agency in Vancouver, Canada, who researches how genetic elements sometimes “jump” around genomes. The work suggests that these viral fossils probably played a key role in the evolution of our species, adds Harmit Malik, an evolutionary biologist at the Fred Hutchinson Cancer Research Center in Seattle, Washington. It’s “a spectacular example of innovation,” he says.