The findings also mean that deer mice may be useful to study coronavirus vaccines, antiviral therapies and infections in the laboratory.
Experts played down the probability that deer mice are harboring the infection in nature, although Tony Schountz, an expert in bat-borne viruses at Colorado State University and a study author, said it is conceivable that a person could give the novel coronavirus to a wild mouse and begin the chain of transmission.
The mice, belonging to the genus Peromyscus, are often studied in biology fieldwork because they are so abundant. In such cases, captured animals may come in close contact with scientists.
“It’s a statistically unlikely event, but I don’t think it’s zero,” Schountz said.
He said he would not be concerned about encounters with mice if a vaccine were developed before the virus becomes endemic in the United States. “But if we don’t get a vaccine … if it’s persisting in nature here in North America, then there’s always going to be that potential risk of contact transmission events from the deer mouse to a human.”
The authors of the second study, by the Public Health Agency of Canada, were circumspect, writing that “the potential for the establishment of Peromyscus rodents as a North American reservoir for SARS-CoV-2 is unknown.”
Observations that these mice are susceptible to the coronavirus “are very convincing,” said Sabra Klein, a microbiologist at the Johns Hopkins Bloomberg School of Public Health who was not involved with this research. But she noted that the preprint status of these reports was an “important aspect to temper too much expectation.”
In the Colorado State University study, researchers infected mice with large amounts of the virus delivered through their noses. Those mice passed the virus to other animals, which in turn passed it to a third group. The second study also showed that infected deer mice passed the virus to one another in experiments performed at the Public Health Agency of Canada’s National Microbiology Laboratory.
“The deer mouse work is actually a really nice example of the type of infectivity studies that are used to experimentally test susceptibility,” said Elinor Karlsson, a professor at the University of Massachusetts Medical School and director of the Vertebrate Genomics Group at the Broad Institute, who was not a member of the research teams.
Early studies in lab conditions should not cause panic about viral spread in the woodlands. “In nature, there’s no evidence today that deer mice are carrying this virus,” Klein said.
She said she was less concerned than the study authors about mouse infections because of what she described as the long-shot chain of events required to expose a wild rodent — an infected person would have to shed enough virus to the ground where a mouse encountered it and became infected.
It’s also unknown whether the large amount of virus used to infect mice in these studies resembles a reasonable real-world exposure, Schountz said.
Scientists know that the coronavirus spilled over into people from an animal host. It most likely originated in bats and possibly infected other creatures on its path from the wilderness to the first human patient zero.
Coronaviruses also have jumped hosts in the opposite direction — from humans to animals — as when people infected camels with MERS. More recently, big cats at a New York zoo tested positive for SARS-CoV-2, which probably was transmitted from an infected zoo worker.
To prevent such transmissions, biologists such as those employed by the U.S. Fish and Wildlife Service are adopting careful approaches to human interaction with wild creatures. The agency, which at the start of the pandemic recommended that scientists avoid research involving contact with bats, is “implementing biosecurity measures” to limit spreading the disease to animals, a USFWS spokeswoman said.
She said biologists are asked to stay home if they feel sick, test positive for the coronavirus or have contact with an infected person. Some researchers are also employing remote sensing tools to monitor wildlife. If people must capture wild animals, they must wear protective equipment and use techniques that minimize contact.
The habitat of deer mice — which belong to different species than the mice seen in medical labs and, sometimes, pantries — ranges from Mexico through most of the contiguous United States to Canada and Alaska. Wild deer mice are already known to be a reservoir of a pathogen called the hantavirus. That virus spreads to people through contact with an infected mouse’s urine, saliva or droppings.
The disease the hantavirus causes in humans has a high mortality rate, but exposure to it is rare, with between 20 and 40 cases reported each year. (Clean up mouse droppings and nests with a bleach solution and gloves rather than brooms or vacuums, experts say, to avoid sweeping particles into the air.)
Animals can get infected with a virus without becoming reservoirs for it. The hantavirus has evolved, for perhaps millions of years, to live within this mouse lineage in North America. The novel coronavirus, a newcomer to the continent, has not — meaning it’s far from certain whether infected mice would help the coronavirus propagate in the environment. “Like humans, nonhuman animals can be dead-end hosts for some viruses,” Klein said.
The susceptibility of deer mice makes them different from the more familiar, all-white lab mice, in which the coronavirus does not replicate well. That’s because the virus binds to a protein, a receptor called ACE2, like a key that slots into a lock. Lab mice have the wrong kind of lock.
Scientists must either mutate the virus to infect mice or mutate the mice — splicing a human lock inside the mouse — so the virus can more easily enter. Researchers in the U.S. Army, for instance, were recently successful at inserting a human ACE2 gene into mice.
Karlsson, the biologist at the University of Massachusetts and the Broad Institute, and her colleagues published a theoretical study of whether the coronavirus could infect 250 species of mammals, based on the abundance of those receptor proteins in the animals. Deer mice, her model suggested, have enough receptors to be vulnerable — a prediction borne out by these laboratory experiments.
That means scientists could, without genetic tweaks, use the deer mice to study the coronavirus. “There is an incredible value to that,” Klein said, “to understand the cells that are being affected and the regions of the lungs.”
At any given time, 1,500 to 2,000 deer mice are being raised at the Peromyscus Genetic Stock Center at the University of South Carolina, the largest supplier of these mice for medical research.
The center’s director, biologist Hippokratis Kiaris, said this potential for coronavirus research has caused an increased demand. “I am aware of several ongoing studies that are trying to expand these findings,” he said.