Bats have a lot of viruses. In fact, bats contain more viral diversity in their leathery-winged legion than just about any mammalian order, with the possible exception of rodents. Besides rabies, they host other deadly viruses that periodically spread to people, like Ebola, SARS, and Nipah virus.
These infections are often fatal for humans, but bats seem to be able to tolerate a lot of them, living their batty lives even while infected with a host of killers. Finding out how bats manage this could hold important insights into the immune system and new ways to treat disease.
Now, researchers from Duke-NUS’s Emerging Infectious Disease (EID) Programme believe they have found a protein that helps bats survive viral infections — and it could possibly be used as a treatment for inflammation in humans.
Bats have more viral diversity in their leathery-winged legion than just about any mammalian order, with the possible exception of rodents — and live with them. Figuring out how may help us find new ways to fight disease.
Inflamed: Inflammation is a natural part of the immune system’s response to infection and injuries. Swelling, redness, pain, warmth, a loss of strength — these are all indicators that the body is battling pathogens or healing damage.
But when inflammation lasts too long — or goes into overdrive — that natural healing process becomes harmful. Chronic inflammation has been connected to an array of diseases and disorders, including gout, rheumatoid arthritis, Parkinson’s, depression, and asthma.
Immune system molecules, called inflammasomes, are known to cause inflammation, and they’re linked to various inflammatory disorders, too. That makes them look like a good target for suppressing harmful inflammation — and bats, it turns out, are really good at that.
Bats, chill: In the Duke-NUS study, published in Cell, the researchers were able to isolate a bat protein, called ASC2, that inhibits inflammasomes and inflammation.
“This suggests that the high-level activity of ASC2 is a key mechanism by which bats keep inflammation under control, with implications for their long lifespan and unique status as a reservoir for viruses,” Matae Ahn, a research fellow at the EID Programme and study first author, said.
And it works outside of bats, too.
First, the team genetically engineered some mice to make bat ASC2 and then tested how they would respond to different diseases.
They found that bat ASC2 “reduced the severity of the diseases driven by various triggers, including viruses,” Vivian Chen, co-first author and Duke-NUS MD/PhD candidate, explained.
Researchers were able to isolate a bat protein, called ASC2, that inhibits inflammasomes and inflammation, providing possible leads for future treatments.
The protein “dampened inflammation induced by multiple viruses,” reduced the mice’s risk of dying from the flu, and even prevented inflammasome activation from the COVID-19 virus. It also appeared to reduce the severity of inflammation from gout crystals — a cause of painful arthritis.
It turns out that four specific amino acid changes make bat ASC2 better at controlling inflammasomes than its human counterpart, providing more possible leads for future anti-inflammatory drug development. Investigating how to use these results to help treat people is the next step, senior author and EID professor Wang Lin-Fa said.
“Bats have attracted great attention as a likely reservoir of the SARS-CoV-2 virus responsible for the COVID-19 pandemic,” Wang, an expert in bat immunology, said.
“But this unique ability to host yet survive viral infections could also have a very positive impact on human health if we can understand and exploit how they achieve this.”
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