A billion-year arms race against viruses shaped our evolution

Viruses and their hosts have been at war for more than a billion years. This battle has driven a dramatic diversification of viruses and of host immune responses. Although the earliest antiviral systems have long since vanished, researchers may now have recovered remnants of one of them embedded, like a fossil, in human cells. A protein called Drosha, which helps to control gene regulation in vertebrates, also tackles viruses, researchers report today in Nature¹. They suggest that Drosha and the family of enzymes, called RNAse III, it belongs to were the original virus fighters in a single-celled ancestor of animals and plants. “You can see the footprint of RNAse III in the defence systems through all kingdoms of life,” says Benjamin tenOever, a virologist at Icahn School of Medicine at Mount Sinai in New York and lead author of the paper.

Plants and invertebrates deploy RNAse III proteins in an immune response called RNA interference, or RNAi. When a virus infects a host, the proteins slice the invader’s RNA into chunks that prevent it from spreading. But vertebrates take a different approach, warding off viruses with powerful interferon proteins — while Drosha and a related protein regulate genes in the nucleus. But in 2010, tenOever witnessed an odd phenomenon: Drosha appeared to leave the nucleus of human cells whenever a virus invaded². “That was weird and made us curious,” tenOever says. His team later confirmed the finding, and saw that Drosha demonstrates the same behaviour in cells from flies, fish and plants. To test the hypothesis that Drosha leaves the nucleus to combat viruses in vertebrates, the researchers infected cells that had been genetically engineered to lack Drosha with a virus. They found that the viruses replicated faster in these cells. The team then inserted Drosha from bacteria into fish, human and plant cells. The protein seemed to stunt the replication of viruses, suggesting that this function dates back to an ancient ancestor of all the groups. “Drosha is like the beta version of all antiviral defence systems,” tenOever says.