New study reveals why bats can carry killer viruses without getting sick

One of the world’s leading experts on emerging infectious diseases has made a key discovery on why bats do not get sick while carrying zoonotic viruses that can prove fatal for humans and other animals.

The findings on bat immunology by Professor Wang Linfa, a biologist who was one of eight scientists to discover that bats were the natural host of the 2003 SARS epidemic, provide important pointers for future medical research on human diseases.

Fresh knowledge on the molecular mechanisms used by bats to suppress viruses including SARS, Middle East Respiratory Syndrome (MERS), Ebola and – most likely – SARS-CoV-2, the pathogen behind the ongoing pandemic, is a vital piece of a puzzle that could ultimately lead to a breakthrough in treatment.

“Professor Wang’s research is all the more important in the context of COVID-19, by contributing to a greater understanding of how zoonotic diseases persist in nature, and potentially aiding new approaches to managing future outbreaks,” said Professor Patrick Casey, Senior Vice-Dean for Research, Duke-NUS Medical School in Singapore.

So far, evidence suggests that the virus that has now infected 43.5 million and killed more than 1.1m worldwide originated in bats, animals that Professor Wang, who now heads the Emerging Infectious Diseases Programme at Duke-NUS, argues have uniquely evolved to harbour dangerous viruses.

His new research provides important confirmation in the long-held theory that, to cope, bats have adopted multiple strategies to reduce pro-inflammatory responses – essentially suppressing their immune systems – to limit the risk of tissue damage and disease.

By contrast, when these viruses make the leap to humans, they can have a deadly and devastating impact.

If the mechanisms used by bats to protect themselves from pathogenic viruses could somehow be replicated in humans, Professor Wang is hopeful that diseases like Covid-19 can be managed to avoid serious conditions or death.

“Suppression of overactive inflammatory responses improves longevity and prevents age-related decline in humans. Our findings may offer potential insights to the development of new therapeutic strategies that can control and treat human infectious diseases,” he said.

“Inflammation is the key,” he told The Telegraph in an interview.

“We know for a fact from human and mouse studies that inflammation is a double-edged sword – when you have the right amount of inflammation it’s protective and when you have too much inflammation or not enough inflammation you get pathogenic disease or death,” said Professor Wang.

“In our pursuit of emerging viruses we have a cliché that very few viruses actually kill us humans and we kill ourselves,” he explained.

Covid-19 was a perfect example, as the same virus could display no or mild symptoms in 80-85 people out of 100 but still kill one person. “It’s a clear indication that it’s the human immune response that makes the difference in the outcome of the infection,” he said.

The research by Professor Wang and his team, produced over the last decade and published this week in the Proceedings of the National Academy of Sciences (PNAS), brings much needed clarity to the enigma of why bats are unaffected by the lethal viruses they hold in their bodies.

The team examined three bat species—the Pteropus Alecto, or black fruit bat, which is native to Australia, the Eonycteris spelaea, or cave nectar bat, found in Southeast Asia, and the David's myotis bat, which is common to China.

In all three, they identified different mechanisms that balance the activity of key proteins that play a major role in mediating immunity and inflammatory responses in mammals, enabling the bats to avoid the detrimental consequences of immune activation.

One of the mechanisms bats use is to reduce the levels of caspase-1, a protein that triggers a key inflammatory cytokine protein, interleukin-1 beta. Another mechanism they employ hampers the maturation of interleukin-1 beta cytokines through a finely-tuned balancing of proteins.

The process of transforming the discovery into life-saving treatments for humans could still take years, said Professor Wang, but the next step of this research has already begun. “It’s a long journey, it’s not easy, but we are definitely going in a new direction,” he said.

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