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Understanding Bats’ Immune Responses and Tolerance to Viral Infections

Researchers from Duke-NUS Medical School studied the mechanisms behind virus tolerance of bats and found changes in regulation of caspase-1 and interleukin-1 beta (IL-1β) pathways, with potential applications for developing age-related therapeutics and for outbreak prevention.

When COVID-19 first emerged, there was much speculation about the origin of the SARS-CoV-2 virus and how it was transmitted to humans. It is believed that the virus hopped over to humans from bats, which are thought to be “reservoirs” for many viruses that have jumped from animals to humans, also known as zoonotic viruses. Besides SARS-CoV-2, bats have been linked to Hendra, Ebola and Nipah viruses as well as rabies and SARS, among many others.

How bats are able to carry and transmit so many zoonotic viruses have baffled scientists for years, especially their ability to carry these viruses without suffering from them – bats carry many viruses, but only the rabies virus is known to be lethal to them. However, when these viruses are passed on to other hosts through biting or contact with bat secretions such as guano, infections in the new hosts can lead to devastating effects.

New research from Duke-NUS Medical School in Singapore may have uncovered information about the immune responses in bats and how they are able to carry many viruses without negative impacts to their own health, and specifically without triggering severe immune responses. These findings were published in the Proceedings of the National Academy of Sciences (PNAS) in October 2020.

The work carried out by Professor Wang Linfa and his laboratory’s researchers from Duke-NUS’ Emerging Infectious Diseases (EID) Programme was based on the identification of mechanisms involving key proteins for the regulation of immune reactions and inflammation in mammals. Three bat species: Pteropus alecto – the black fruit bat, Eonycteris spelaea – the cave nectar bat and Myotis davidii – David’s myotis bat were studied. The team identified mechanisms and studied proteins that regulate immune and inflammatory responses.

It has been hypothesised by several groups that bats experience suppression of their immune responses, allowing them to tolerate viral infections without exhibiting signs of illness. In other organisms, caspase-1 is activated when a danger signal is received, such as the presence of antigens, and cleaves interleukin-1 beta (IL-1β), triggering downstream events that mount an inflammatory response and activate antiviral genes. The researchers observed that in bats, caspase-1 levels were reduced, and IL-1β cytokines were prevented from reaching maturation. These mechanisms essentially reduced the inflammatory response in bats that is usually triggered by viral infections.

Apart from helping scientists understand the mechanisms behind bats’ unique ability to carry viruses without getting sick, these findings could have other medical applications for humans. “Suppression of overactive inflammatory responses improves longevity and prevents age-related decline in humans,” explained Professor Wang. “Our findings may offer potential insights to the development of new therapeutic strategies that can control and treat human infectious diseases.”

As it is believed that SARS-CoV-2 is a zoonotic virus that was first transmitted to humans from bats, this research is especially useful in disease prevention and management. Professor Patrick Casey, who is Senior Vice-Dean for Research at Duke-NUS, explains that “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.” [APBN]