Researchers have identified eight more people who died from the Borna virus, a known pathogen in several animals that was only recently shown to cause disease in humans. Scientists had been skeptical that the virus could infect people, but the new work suggests Borna has been killing humans for decades.
“It’s a nice, clear study,” says Thomas Briese, a molecular virologist at Columbia University who was not involved with the work. The research, he says, adds important data on a human disease that scientists are just beginning to explore.
For more than 300 years, people in central Europe have known of an equine “disease of the head” that leads horses to go blind, lose coordination, and die. The infectious agent responsible, Borna disease virus 1—named for an outbreak in military horses in the German city of Borna in the 19th century—causes encephalitis, an inflammation in the brain. The pathogen also infects sheep, ostriches, and other animals.
Experts have debated whether it afflicts humans for decades. Some scientists have suggested the virus infects many people around the world, causing depression and other psychiatric disorders. But the data were questionable and the field was plagued with contamination problems, Briese says.
In the past few years, a different story has emerged. Scientists identified the bicolored white-toothed shrew (Crocidura leucodon) as a natural reservoir of the virus: The animals carry it with no apparent illness. And they found a handful of people in Germany with severe encephalitis caused by the virus.
In the new study, researchers screened brain tissue from 56 encephalitis patients over the past 25 years that had been stored at the University Hospital in Regensburg, Germany. For 28 patients, the cause of the encephalitis was known—cancer or autoimmune disease, for example—and none of these control tissue samples was positive for Borna virus. But of the 28 patients for whom no cause of the encephalitis could be found, seven carried the virus in their brain, the researchers report today in The Lancet Infectious Diseases.
The scientists identified two further cases in other medical centers in southern Germany. For seven of these eight new patients (one of the Regensburg patients had been previously reported), the researchers managed to sequence the genome of the virus. The viruses taken from each patient closely resemble genomes isolated from animals in the area where the patients lived. But they differ from each other enough that each infection occurred independently from wildlife, instead of the pathogen being transmitted between people, the team concludes.
How exactly the virus makes it into a person is still unclear. “This is now one of the big questions we need to answer,” says study author Martin Beer, a virologist at Germany’s Federal Research Institute for Animal Health. Five of the eight patients owned cats, he notes, and at least two of the felines reportedly brought home small mammals, including shrews.
“People might dispose of the animals with their bare hands and then rub their eyes,” says Norbert Nowotny, a virologist at the University of Vienna, who has studied Borna virus for decades but who was not involved with the current work. Identifying more cases could help resolve how the virus is transmitted, he says.
As testing for the virus becomes more common in the affected regions, scientists are discovering more cases. In October 2019, an 11-year-old girl in Bavaria died of encephalitis, and a postmortem exam found Borna virus in her brain. The absolute number of cases is likely to remain low, Beer says. But the virus may account for a significant number of unexplained, fatal encephalitis cases in the parts of Germany, Austria, and Switzerland, where the pathogen is endemic.
Identifying more cases could also give a better estimate of how often the infection is fatal, Nowotny says. Of the 14 cases reported in the scientific literature so far, 11 have died. “I imagine that as we identify more cases we will also find more mild cases.”