The discovery is no cause for alarm, said Dr. Robert H. Yolken, a virus expert at the Johns Hopkins Children's Center, but it's certainly odd: A bug known before only to infect green algae appears to have jumped from the plant to the animal kingdom, landing in the human throat.
Without infecting people, this bug, or at least its DNA footprint, appears to make trouble, although not so much that the 40 healthy people who turned out to be harboring it noticed anything amiss. It took a test to find an effect in humans, then to corroborate the results in mice, ultimately linking the algae virus traces to slightly diminished mental functions, including attention, spatial orientation and memory.
Published last month online in the Proceedings of the National Academy of Sciences, the research by Yolken and 17 co-authors is another drop in a growing sea of information on the microorganisms living in our bodies and how they may affect us. The microbiome, as it's called, contains roughly 10,000 species of organisms and consists of about 10 times as many cells as the human body. Taken together, their collective weight is put at up to three pounds, equal to a human brain.
Elements of this vastly complicated entity that has been viewed as another body organ, or even another genome, have been identified as suspected risk factors in several conditions, including obesity, autism, depression and schizophrenia.
Humans evolved alongside the organisms that make up the microbiome, he explained, and, for the most part, have developed a healthy working relationship with them. While this is the first time that traces of the algae virus have been found in people's throats — there was an earlier report of this virus' DNA showing up in a vaginal sample — the virus has not been found intact in people, or to be replicating itself in human cells or infecting anyone.
Plant viruses have been known to replicate themselves in insects, but not in animals, said James L. Van Etten, a professor of plant pathology at the University of Nebraska, and a co-author of the recent research report. Such a discovery would be exciting, he said, but "I think it's highly unlikely."
The research, however, does suggest a link between a virus and brain function. That possible connection is a specialty for Yolken, who directs the Stanley Division of Developmental Neurovirology at Johns Hopkins Hospital.
Their examination some years ago of brain tissue samples turned up traces of DNA that they did not immediately recognize. A search led Yolken and his researchers to a bug called chlorovirus ATCV-1, known only to infect green algae. That led them to Van Etten, an authority on this virus.
Van Etten recalled receiving an email from Yolken on a Sunday, and thinking someone was kidding.
"You're working with big DNA viruses that infect algae and someone tells you it has something to do with a brain disorder, the chances of that seem very slim," Van Etten said. "I thought one of my friends was jerking me around."
What he thought was a prank led to years of serious work.
After finding the algae DNA in the brain samples, the researchers took throat swab samples from 92 adults who had no psychiatric or physical disorders. Forty samples, 43 percent, showed the chlorovirus DNA.
As all 92 men and women tested already were taking part in a cognitive function study, the researchers tested for a possible connection between the presence of the algae virus DNA and diminished mental performance.
They found a link. Those people with traces of the viral DNA did not perform as well as others in tests measuring attention span and their speed in drawing a line between a sequence of numbered circles on a piece of paper.
The differences were small, not enough to impair the person's ability to function, but measurable, Yolken said.
An equal number of male and female mice — some infected with the virus, some not — showed similar results in tests measuring the mouse equivalent of human cognition. These included testing the mice for their ability to navigate a maze, recognize a new point of entry to the maze and pay attention to a new object introduced to their environment.
The mouse study, which used live green algae virus, provided "strong" evidence for the possibility that the virus was present in the people, Yolken said. The mouse test also suggests that mammals can go through "at least some stages of infection with ATCV-1 under experimental conditions," Yolken said.
William T. Carpenter Jr., a professor of psychiatry and pharmacology at the University of Maryland School of Medicine who was not involved in this research, called the result compelling.
"It's feasible to suppose that this virus could have an effect on cognition," Carpenter said.
In the relatively new field of the microbiome, and the study of the viral roots of psychiatric disorders, there are many more questions than answers. In this case, it's still not clear how traces of the algae virus ended up in these people.
Van Etten said such viruses are common in freshwater ponds, and would cling to a swimmer's skin, but it seems unlikely that nearly half of these 92 people had been swimming recently in a pond. He said it's possible that the virus could be present in some other microorganism. Algae need sunlight to live, he said, so they're not likely to survive inside a human throat.
One next step in this work is to try to find the complete virus in people. For that study, Yolken said, researchers would try to grow the virus in its natural host, green algae, from samples taken from the human throat. They're also working on a way to identify an immune response to the virus in the blood of humans.
Yolken emphasizes that so far, elements of the microbiome have only been identified as risk factors, not a direct cause, in human disorders such as obesity, and psychiatric illness. Those links have not yet been established.
"We do think this is an area that needs to be explored," Yolken said. "And explored a lot more."