AsianScientist (Mar. 8, 2019) – An international research team has identified molecular and genetic mechanisms that allow bats to stay healthy while hosting viruses that kill other animals. The findings are published in Nature Microbiology.
Bats have long lifespans and host numerous viruses, such as the Ebola virus and the severe respiratory syndrome (SARS) coronavirus, that are extremely harmful when they infect humans and other animals. How bats themselves appear relatively unaffected by their virus burden has been a mystery.
In the present study, researchers at Duke-National University of Singapore (NUS) Medical School and colleagues found that bats can harbor infections without suffering pathological effects due to their ability to limit inflammation. 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.
In contrast, bats do not react to infection with the typical inflammatory response that often leads to pathological damage. This is because NLRP3—the inflammation sensor that normally triggers the body’s response to fight off stress and infection—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,” said Dr. Matae Ahn at Duke-NUS Medical School, the first author of the study.
The researchers compared the responses of immune cells from bats, mice and humans to three different RNA viruses—the influenza A virus, the Middle East Respiratory Syndrome coronavirus and the Melaka virus. The inflammation mediated by NLRP3 was significantly reduced in bats compared to mice and humans.
Probing deeper, the scientists found that ‘transcriptional priming,’ a key step in the process to make NLRP3 proteins, was reduced in bats compared with mice and humans. They also identified unique variants of NLRP3 only present in bats that render the proteins less active in bats than in other species. These variations were observed in two very distinct species of bats—Pteropus alecto, a large fruit bat known as the Black Flying Fox, and Myotis davadii, a tiny vesper bat from China.
The results indicate that bat-specific variants of NLRP3 have been genetically conserved through evolution, further confirmed by comparisons between 10 bat and 17 non-bat mammalian NLRP3 gene sequences.
Hence, rather than having a better ability to fight infection, bats have a much higher tolerance for it, said the researchers. The dampening of the inflammatory response actually enables infected bats 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,” said Professor Wang Lin-Fa of Duke-NUS Medical School, a senior author of the study. “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.”
The article can be found at: Ahn et al. (2019) Dampened NLRP3-mediated Inflammation in Bats and Implications for a Special Viral Reservoir Host.
Source: Duke-NUS Medical School; Photo: Pixabay.
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