For millions of years, various types of coronavirus have thrived in hundreds of bat species without causing any harm. But when they’ve occasionally jumped to humans—as was the case with SARS in 2003 and SARS-CoV-2 last year—they caused havoc, suggesting that at least some people’s immune systems lack antiviral defences present in bats.

Scientists are now looking to genomes of bats for clues about how these animals fight off coronaviruses. “We could potentially take what we learn from bats and apply it to humans,” says Erich Jarvis, a professor at The Rockefeller University. For example, he hopes that this research will reveal weaknesses in the human immune system’s response to infection, or help explain why some infected people get the life-threatening disease while others experience little to no symptoms.

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But genetic differences between species can be incredibly subtle. To find them, Jarvis is using high-precision sequencing techniques to produce accurate genetic data for different bats species.

“What we have been seeing in the currently available genetic data is that for many of the species, some genes are incompletely put together or put together incorrectly because of poor quality of the genome assemblies,” says Jarvis, a Howard Hughes Medical Institute investigator. “So the first step is to fix that problem.”

Sources of exceptional immunity

Studying coronavirus is a major shift for Jarvis, whose research typically focuses on language. He studies the neural and genetic mechanisms that enable only a few species, like humans and songbirds, to communicate vocally. But at the outset of the COVID-19 pandemic, he diverted his expertise and applied the same methods to instead to see if they could crack the mystery of bats’ exceptional immunity to coronavirus. His group began by sequencing the genome of the horseshoe bat, thought to be the initial host of SARS-CoV-2, and the pangolin, which may have been an intermediary host.

One initial target for their investigation is the ACE2 receptor, which sits on the surface of cells in bats, humans, and many other vertebrates, and is hijacked by the coronavirus as an entrance. Deciphering the receptor’s exact structure could reveal why horseshoe bats are more resistant to the virus than humans, and potentially, even explain why some humans are more resistant than others.

But the search goes beyond the ACE2 receptor. “There are likely a number of genes involved in how each species responds to the virus, and to find them, we need to scan the entire genome,” Jarvis says.

Some clues have already started to emerge. In a recent study published in Nature, Jarvis and his collaborators created complete genome assemblies of six species of bats and looked for genes that were consistently selected during the evolution of these species, meaning that they likely offered some important benefits to the animals.

Their search turned up a number of genes linked to exceptional bat behaviours such as flight and echolocation as well as others related to the immune system. The researchers found a unique pattern of evolution among the immune-related genes suggesting that the bats have acquired more and more of those linked to antiviral defences over the millennia.

Further examining this subset of genes may speed the discovery of human immune mechanisms involved in battling the coronavirus, researchers say, and could potentially lead to novel treatments.

Source: Rockefeller University

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