A new study identifies the molecular and genetic mechanisms that allow bats to stay healthy even when hosting viruses that kill other animals, including humans.
Bats live long and host numerous viruses, including Ebola virus, Nipah virus, and severe acute respiratory syndrome and Middle East respiratory syndrome (MERS) coronaviruses, which are all extremely harmful when they infect humans and other animals.
Researchers wanted to find out how bats can harbor so many of these pathogens without suffering from diseases themselves.
The key? Bats don’t react to infection with the typical inflammatory response that often leads to pathological damage. In humans, while this inflammatory response helps fight infection when properly controlled, it also contributes to the damage infectious diseases cause, as well as to aging and age-related diseases when it goes into overdrive.
Tamped down inflammation
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.
“Bats’ natural ability to dampen inflammation caused by stress and infection may be a key mechanism underlying their long lifespans and unique viral reservoir status,” says Matae Ahn, an MD/PhD candidate of the Emerging Infectious Diseases Program at Duke-NUS Medical School and first author of the study, which appears 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. Bats showed significantly reduced levels of inflammation when compared to mice and humans.
Digging further, the researchers found reduced levels of “transcriptional priming,” a key step in the process to make NLRP3 proteins, in bats compared with mice and humans.
They also found unique variants of NLRP3 that render the proteins less active in bats than in other species. They observed these variations in two very distinct species of bats—a large fruit bat known as the Black Flying Fox (Pteropus Alecto) and Myotis davadii, a tiny vesper bat from China—indicating the variants have lasted through evolution.
Anti-disease not anti-pathogen
Further analysis comparing 10 bat and 17 non-bat mammalian NLRP3 gene sequences confirmed that the adaptations appear to be bat-specific.
What this implies, the researchers say, 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.
“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,” says senior author Wang Lin-Fa, director of the Emerging Infectious Diseases Program.
“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.”