Some of the planet’s scariest, most lethal viruses find a natural refuge inside bats, including Ebola, rabies, Marburg and the SARS coronavirus. Many high-profile epidemics have been traced to bats, and scientists are discovering new bat-borne viruses all the time.
The animals seem especially adept at harboring and spreading disease. Scientists trying to understand why have found some promising leads in bat genomes, but others argue bats’ notoriety as viral carriers isn’t justified.
“Are bats special? I still say it’s too early to answer,” says Linfa Wang, who leads research groups at CSIRO’s Australian Animal Health Laboratory and the Duke-NUS Graduate Medical School in Singapore. He's spent the last two decades studying bat-borne viruses and hunting for characteristics that might make the animals such great viral hosts.
“The question is so important we just can’t ignore it anymore,” he says.
Bats and other species that chronically harbor viruses, such as rats or mice, are known as disease reservoirs. Most of the time, these reservoirs stay intact, with infected animals rarely showing symptoms of disease. But sometimes they leak, letting a virus infect new, much more vulnerable species. This is almost certainly what happened with the ongoing Ebola outbreak in West Africa, which began with a trickle in December and has since infected at least 8,900 people and killed more than 4,400. Scientists suspect bats are to blame for this epidemic, which has overwhelmed Guinea, Sierra Leone, and Liberia.
Anecdotally, bats certainly appear to carry a disproportionately high number of scary viruses. But whether this is actually true remains an open question.
Scientists essentially fall into two camps on this issue. One school of thought says bat-related epidemics are simply a numbers game; the idea is there are so many species and so many individuals that the emergence of bat-borne illnesses isn’t surprising. The other suggests bats are indeed special, that there’s something about their physiology or their lifestyle that makes them exceptionally good viral repositories.
What that something is has yet to be determined, but Wang and his colleagues have spent a good chunk of time trying to sort it out. They began by looking at bat genomes, hoping to find a clue in the bats’ immune system, like a set of genes that only bats have.
Last week, authorities in Spain euthanized a dog whose owner had become infected with Ebola after treating a missionary who’d been in West Africa. Many argued the response was extreme and unwarranted, citing a lack of evidence dogs can transmit Ebola.
During the 2001-2002 Gabon outbreak, researchers found roughly 25 percent of the dogs from villages with human Ebola cases tested positive for Ebola antibodies. But dogs from villages without human cases also tested positive. And so did two dogs in France that presumably never encountered anything carrying the virus. None of the animals became symptomatic or died, so the question remains open as to whether dogs can be infectious.
Tracing the routes from reservoir to humans is tricky. Even now, scientists don’t know all the pathways Ebola can take from bats to humans. One known mode of transmission is eating an infected animal. Bats, primates, and other wildlife often are consumed in parts of West Africa. Now, people are being warned about the risk of consuming bushmeat.
Other pathways are less clear. Saliva, urine or feces from infected fruit bats could contaminate fruit that might then be eaten by a human, or intermediate host. This can be the case with Nipah and Hendra viruses. In Bangladesh, Nipah virus appears to pass directly from bats to humans via date palm sap. In Southeast Asia, Nipah first infects pigs, which then infect humans. In Australia, Hendra appears to use horses as an intermediate species. And Ebola has infected primates that people then eat.
Instead, the team uncovered a more subtle difference: Even though bat genomes contain many of the same ingredients as other mammals, bats use them differently. In particular, the bat genes coding for proteins that detect and repair damaged DNA are much more prevalent than expected. More simply, those genes are believed to be doing something that helps the bats survive and reproduce, so that those genes are passed on to subsequent generations.
These results, reported in the journal Science in December 2012, correspond with the previous observation that DNA damage repair genes are frequent targets for invading viruses, which could be what is applying the evolutionary pressure. The findings also mesh with the anecdotal observation that bats rarely (if ever) develop tumors—perhaps because the repair genes can outpace any malignant growth.
Since then, Wang and his colleagues have gone a step further. Newer, still-unpublished findings suggest that unlike in humans or mice, where defenses such as anti-tumor and anti-viral genes are activated only in response to a threat, in bats these genes seem to be perpetually turned on. That activity keeps levels of any harbored viruses simmering below the point at which they could cause harm. In other words, evolution has conspired to turn bats’ surveillance mechanisms up to 11.
As for why, Wang suggests a link with flight, which boosts a bat’s metabolic rate to a level many times higher than when it is resting. Such sustained energy production generates stress that can damage cells and DNA if it isn’t quickly detected and repaired.
So perhaps initially, those damage-repair proteins got turned way up to combat the damage caused by bats doing what bats do, which is flying around every night. If true, the ability to carry lethal viruses might have come second, as a sort of coevolutionary accident, Wang says.
Another hypothesis, reported in *Emerging Infectious Diseases *in May, suggests bat flight might generate enough heat to mimic a fever. As part of the normal immune response in many animals, fevers help combat infection by raising body temperature to levels that will kill or disable invading pathogens. By raising their temperatures, the hypothesis suggests, flying might inadvertently be dialing back bats’ viral load each night.
Though no experiments have been done to test the idea, some scientists say it’s plausible that one reason bat-borne viruses are so lethal when they spill over into humans or other animals is because they’ve evolved to withstand the bat’s especially active immune system.
“We don’t have that sort of immune system,” says Angela Luis, a disease ecologist at the University of Montana, and an author of the fever-flight study. Once free from the bat’s hyper-vigilant, perpetually turned on defenses, those viruses might have no problem overwhelming more feeble immune systems.
Wang isn’t yet ready to conclude bats are especially good viral hosts, but believes the scientific field is creeping closer to accepting that possibility.
The other possibility is that what’s happening is simply a combination of numbers and opportunity, that bat-borne spillovers are nothing more than statistics at work.
With more than 1,200 known species, bats comprise more than 20 percent of the mammal species on Earth. And among mammals, they’re outnumbered only by rodents (contrary to popular belief, bats are not rodents). But in many areas, bats are more numerous than rodents, with millions of individuals sometimes living in a single colony.
The perception that bats are somehow special may be colored by high-profile outbreaks and a disproportionate amount of work focused on bats as viral vessels. “The self-fulfilling prophecy, which I would warn against, is that the more we dig, the more viruses we’re going to find,” said Kevin Olival, a disease ecologist at EcoHealth Alliance.
In a 2013 study, Olival and colleagues examined the virome of a giant bat called the Indian flying fox (Pteropus giganteus). In that one species, they detected 55 viruses, 50 of them previously unknown. That’s roughly the total number of bat viruses identified in a seminal 2006 study that reviewed all of the relevant research done at the time. In the intervening eight years, though, that number has doubled or tripled or more, depending upon the criteria used to define “known virus.”
But Olival argues that trend is not unique to bats. “If you look at the broad spectrum of what we know about mammal virus diversity, all have pretty diverse groups of viruses,” he said. “The groups that don’t are the ones we haven’t looked at enough.”
The question, then, is why do we keep hearing about bat-borne epidemics?
"I think the important thing is ecology, and thinking about where these animals live, and how humans are coming into contact with them,” Olival says. He suggests that what's really important is the way humans interact bats -- or rather, the ways in which humans are interacting with and encroaching upon bat habitat.
