As world reels from the coronavirus pandemic, bats are harboring a far deadlier disease, show studies
It's no coincidence that some of the worst viral disease outbreaks in recent years -- severe acute respiratory syndrome (SARS), the Middle East respiratory syndrome (MERS), Ebola, Marburg and likely the new coronavirus -- originated from bats.
Bats are the natural reservoirs of a number of high-impact viral zoonoses: they host at least 61 viruses that can infect humans. And while rodents hugely outnumber bats, bats are more likely than rodents to carry viruses that can be transmitted between animals and humans, according to research by Colorado State University.
In the study, published in Proceedings of the Royal Society B – Biological Sciences, researchers compiled databases of viruses in bats or rodents and the species in which each has been detected. They found that bats host, on average, significantly more zoonotic viruses per species than rodents. Zoonotic diseases are illnesses that can spread between animals and people. Viruses (both zoonotic and non-zoonotic) had a broader host range in bats -- averaging 4.51 bat host species per virus, whereas rodent viruses averaged 2.76, shows analysis. This simply means that each bat virus, on average, infects 4.51 bat species, while each rodent virus infects 2.76 rodent species.
“There’s been a lot of speculation that bats might be special in some way as far as their potential to host zoonotic diseases. We found that although there are twice as many rodent species as there are bat species, bats hosted more zoonotic viruses per species than rodents,” says study author Angela Luis in a statement.
According to experts, bats carry SARS, Ebola, Nipah and Hendra viruses – all of which can be deadly to humans. The researchers found that bats were more likely to share viruses such as these between species and that viruses may pass more easily between different bat species that live in the same geographic range than between rodent species.
Why are bat viruses so deadly and why don’t they get sick?
Scientists from China had warned in 2019 that it is highly likely that future coronavirus outbreaks will originate from bats and that there is an increased probability that it will occur in China. Based on their review, four experts from China had cautioned that the investigation of bat coronaviruses becomes an urgent issue for the detection of early warning signs, which, in turn, minimizes the impact of such future outbreaks in China.
But what makes bats so dangerous? Bats host virulent zoonotic viruses without experiencing disease. According to researchers, bats' fierce immune response to viruses could drive viruses to replicate faster, so that when they jump to mammals with average immune systems, such as humans, the viruses wreak deadly havoc.
According to the study by experts from the University of California (UC), Berkeley and other institutes, some bats -- including those known to be the original source of human infections -- have been shown to host immune systems that are perpetually primed to mount defenses against viruses. Viral infection in these bats leads to a swift response that “walls the virus out of cells.” While this may protect the bats from getting infected with high viral loads, it encourages these viruses to reproduce more quickly within a host before a defense can be mounted, says the analysis published in eLife.
This makes bats a unique reservoir of rapidly reproducing and highly transmissible viruses. While bats can tolerate viruses like these, when these bat viruses then move into animals that lack a fast-response immune system, the viruses quickly overwhelm their new hosts, leading to high fatality rates, say researchers. “Some bats are able to mount this robust antiviral response, but also balance it with an anti-inflammation response. Our immune system would generate widespread inflammation if attempting this same antiviral strategy. But bats appear uniquely suited to avoiding the threat of immunopathology,” says said Cara Brook, a postdoctoral Miller Fellow at UC Berkeley and the first author of the study, in the study.
Heightened environmental threats to bats may add to the threat of zoonosis. The researchers caution that disrupting bat habitat appears to stress the animals and makes them shed even more virus in their saliva, urine and feces that can infect other animals.
“The bottom line is that bats are potentially special when it comes to hosting viruses. It is not random that a lot of these viruses are coming from bats. Bats are not even that closely related to us, so we would not expect them to host many human viruses. But this work demonstrates how bat immune systems could drive the virulence that overcomes this,” says study author Mike Boots, a disease ecologist and UC Berkeley professor of integrative biology, in the analysis.
Yet another study by an international research team led by Duke-NUS Medical School, Singapore, identifies molecular and genetic mechanisms that allow bats to stay healthy while hosting viruses that kill other animals.
Researchers wanted to find out how bats can harbor so many of these pathogens without suffering from diseases. The key, they found, is in the bat's ability to limit inflammation. Bats do not react to infection with the typical inflammatory response that often leads to pathological damage. In humans, while the inflammatory response helps fight infection when properly controlled, it has also been shown to contribute to the damage caused by infectious diseases, as well as to aging and age-related diseases when it goes into overdrive.
“The inflammation sensor that normally triggers the body's response to fight off stress and infection, a protein called NLRP3, barely reacts in bats compared to humans and mice, even in the presence of high viral loads,” says the study published in Nature Microbiology.
The researchers compared the responses of immune cells from bats, mice and humans to three different RNA viruses -- influenza A virus, MERS coronavirus, and Melaka virus. The inflammation mediated by NLRP3 was significantly reduced in bats compared to mice and humans.
What the analysis reveals is that rather than having a better ability to fight infection, bats have a much higher tolerance for it. The “dampening of the inflammatory response” actually enables them to survive, says the team.
"Bats appear to be capable of limiting excessive or inappropriate virus-induced inflammation, which often leads to severe diseases in other infected animals and people. Our finding may provide lessons for controlling human infectious diseases by shifting the focus from the traditional specific anti-pathogen approach to the broader anti-disease approach successfully adopted by bats,” says senior author of the study Professor Wang Lin-Fa, Director of Duke-NUS' EID Programme, in the analysis.
Many experts believe that the COVID-19 virus was passed from bats to a mystery animal species that then passed it on to people. So far, over 37,680 have died in coronavirus pandemic, and over 784,710 have fallen sick globally.
Vigorous flight leads to longer lifespan and perhaps viral tolerance
In the 2019 study, authors write that bats are the only mammals with the capability of powered flight, which enables them to have a longer range of migration compared to land mammals. Bats are also the second-largest order of mammals, accounting for about a fifth of all mammalian species, and are distributed globally.
“It is hypothesized that flight provided the selection pressure for coexistence with viruses, while the migratory ability of bats has particular relevance in the context of disease transmission. Indeed, bats were linked to a few highly pathogenic human diseases, supporting this hypothesis,” said the study.
According to the UC Berkeley study, as the only flying mammal, bats elevate their metabolic rates in flight to a level that doubles that achieved by similarly sized rodents when running.
“Generally, vigorous physical activity and high metabolic rates lead to higher tissue damage due to an accumulation of reactive molecules, primarily free radicals. But to enable flight, bats seem to have developed physiological mechanisms to efficiently mop up these destructive molecules,” says the analysis.
This has the side benefit of efficiently “mopping up damaging molecules produced by inflammation of any cause,” which may explain bats' uniquely long lifespans. Smaller animals with faster heart rates and metabolism typically have shorter lifespans than larger animals with slower heartbeats and slower metabolism, presumably because high metabolism leads to more destructive free radicals. But bats are unique in having far longer lifespans than other mammals of the same size: some can live 40 years, whereas a rodent of the same size may live two years, says the research team.
“This rapid tamping down of inflammation may also have another perk: tamping down inflammation related to antiviral immune response. One key trick of many bats' immune systems is the hair-trigger release of a signaling molecule called interferon-alpha, which tells other cells to "man the battle stations" before a virus invades,” they say in their analysis.
The researchers noted that many of the bat viruses jump to humans through an animal intermediary. SARS got to humans through the Asian palm civet; MERS via camels; Ebola via gorillas and chimpanzees; Nipah via pigs; Hendra via horses and Marburg through African green monkeys. “Nonetheless, these viruses still remain extremely virulent and deadly upon making the final jump into humans,” says the team.