Bats live enigmatic lives on many fronts – they echolocate prey, nap upside-down, and can act as viral reservoirs without obvious signs of disease themselves. It’s no wonder they’ve achieved attention over the years for their role in rabies, Hendra and Nipah henipaviruses, Ebola and Marburg filoviruses, and SARS coronavirus. But perhaps there is more to this story than we’ve been crediting these nimble flyers.
To delve deeper into the mystery of how bats continue to thrive as viral incubators, researchers from the University of California, Berkeley, used a combination of in vitro experimentation and within-host modeling. They found critical bits of new information.
Bats have immune systems that are primed and ready to combat infection by walling the virus out of cells. Such a high immune response helps the bats but also encourages a swift spread; it’s highly transmissible yet not destructive to them individually. Animals with more sluggish immune systems are more likely to be overwhelmed by the virus. Certain bat species, on the other hand, can simultaneously mount a robust antiviral and anti-inflammation response.
"This would result in widespread inflammation if another mammal were to attempt such an antiviral response with their immune system. Bats appear to have highly upregulated anti-inflammatory pathways," Cara Brook, a postdoctoral Miller Fellow at UC Berkeley and first author of the study published in eLife, told IFLScience. "They have this kind of yin and yang of robustness and viral defenses that are then balanced by anti-inflammatory pathways."
Another trick up their wing may involve a signaling molecule called interferon-alpha that helps warn cells in advance of viral infection before it can attack them. To test this, the team challenged cultured cells from the immune systems of an Egyptian fruit bat, an Australian black flying fox, and an African green monkey (as a control).
The differences in response were stark: the monkey cells were completely overwhelmed by the viral invader. The Egyptian fruit bat fared better, its interferon kickstarting an early warning system. The real winner, though, was the Australian black flying fox cells, which slowed the viral infection and allowed it to last longer, all while allowing the cells to survive.
"When you have a higher immune response, you get these cells that are protected from infection, so the virus can actually ramp up its replication rate without causing damage to its host," said Brook. "But when it spills over into something like a human, we don't have those same sorts of antiviral mechanism, and we could experience a lot of pathology."
To make matters worse (for us, that is), stressed-out bats may shed the virus faster through their saliva, urine, and feces production. This can go on to infect other animals as intermediary hosts before infecting humans. Such evidence suggests heightened environmental threats may add to the threat of zoonosis.
The team propose the bats’ metabolic rates in flight may be the reason why they are “special when it comes to hosting viruses.” Instead of greater tissue damage as typically seen in high physical activity and metabolic rates, bats have developed physiological mechanisms to combat this. It’s possible these same mechanisms are also in gear when they become infected with a virus, reducing damage from inflammation. In fact, bats have far longer lifespans than many mammals of the same size.
"A bat in flight will elevate its baseline metabolic rate up to 15 times, which is more than double that a terrestrial animal would do going from resting to running. We think that to make that evolutionarily possible, bats had to develop these hyper-efficient anti-inflammation pathways that then had cascading consequences on longevity and antiviral immunity," said Brook.
The purpose of this work isn’t to demonize bats but to learn from their ingenuity and understand the trajectory of an infection. "I want to highlight that bats often get a bad reputation as the sources of these viral zoonoses and while the threat is real, I also think it is important to point out that a lot of these emergence events are happening with increasing frequency that results from land conversion and higher contact with wildlife," said Brook.
"I think there is a win-win solution for bat conservation and public health that involves maintaining intact habitat and efforts that can both preserve wild bat populations and also help avoid future zoonosis."