The viruses we know best are the ones that make us sick — the influenza viruses that send us to bed and the smallpox viruses that may send us to the grave.
But healthy people are rife with viruses that don’t make us ill. Scientists estimate that tens of trillions of viruses live inside of us, though they’ve identified just a fraction of them. A vast majority are benign, and some may even be beneficial. We don’t know for sure, because most of the so-called human virome remains a mystery.
This year, five universities are teaming up for an unprecedented hunt to identify these viruses. They will gather saliva, stool, blood, milk and other samples from thousands of volunteers. The five-year effort, called the Human Virome Program and supported by $171 million in federal funding, will inspect the samples with artificial intelligence systems, hoping to learn about how the human virome influences our health.
“I think it will swamp the data that we’ve had up until now,” said Frederic Bushman, a microbiologist at the University of Pennsylvania and one of the program’s leaders.
The first hints of the human virome emerged over a century ago. Analyzing stool samples, scientists discovered viruses known as phages that could infect bacteria inside the gut. Phages also turned up in the mouth, lungs and skin.
Scientists later found viruses that infected our own cells without causing any major symptoms. A vast majority of the world’s population gets infected with cytomegaloviruses, for example, which can colonize just about every organ.
In the early 2000s, new genetic sequencing methods led scientists to find yet more viruses in saliva, blood and stool. The technology also allowed them to estimate the number of viruses in our bodies by counting copies of viral genes. Each gram of stool, it turned out, contains billions of phages.
Each person’s gut may harbor hundreds or even a thousand species of phages. But when biologists go from person to person, they will find many viral species in one that are missing from another — even when those people are married. The more people scientists study, the more species of phages they discover.
“I’m expecting tens of millions of species,” said Evelien Adriaenssens, a phage biologist at the Quadram Institute in Norwich, England.
The viruses that infect human cells have turned out to be unexpectedly diverse. In 1997, researchers in Japan inspecting the blood of a patient discovered an entirely new virus family that came to be known as anelloviruses. Last month, a study revealed over 800 new species of anelloviruses, bringing the total number of known species to more than 6,800.
Some recent studies about the human virome raise questions about the very definition of a virus. A standard virus consists of a protein shell holding genes that are encoded either in double-stranded DNA or single-stranded RNA. But scientists are finding that our bodies are also home to exquisitely tiny rings of free-floating RNA.
Scientists are still blind to much of the human virome. Viruses are so small that they can lurk unseen inside cells. Some can even sneak their genes into their host cell’s DNA, where they can hide for years before replicating.
“Totally new tools are going to have to come in,” said Dr. Pardis Sabeti, a computational biologist at the Harvard T.H. Chan School of Public Health.
Dr. Sabeti and her colleagues are developing an artificial intelligence system that the Human Virome Program will deploy to discover subtle features of viral genes.
The researchers will then try to figure out what all those viruses are doing inside of our bodies. Scientists have traditionally treated phages like predators of bacteria, ruthlessly killing them in order to make more copies of themselves. But recent experiments are pointing to a much more complicated relationship.
“They’re not in a fight to the death,” said Colin Hill, a microbiologist at APC Microbiome Ireland, a research center in Cork. “They’re in a partnership.”
In the human body, for example, phages typically don’t exterminate their host bacteria. And bacteria may benefit from their friendly relationships with phages, which can move genes from one host microbe to another, possibly boosting their survival.
This partnership may be good for our health, too. Recent studies suggest that phages distribute defensive genes that their hosts can use to hold back the invading pathogens. And cytomegaloviruses might help defend us against skin cancer.
Dr. Shadmehr Demehri, a Harvard cancer immunologist, and his colleagues have found evidence that cytomegaloviruses become active inside skin cells that have been damaged by the sun. The infected cells make viral proteins, which draw the attention of nearby immune cells. They attack the damaged cells — and may thus prevent them from progressing to cancer.
Dr. Demehri’s studies have shown that human papillomaviruses, too, can help destroy skin cells that are at risk of producing a tumor.
“It’s a paradigm shift in how we think of viruses in general,” Dr. Demehri said.
