Bats, the only flying mammal, carry a variety of viruses, many of which are zoonotic. Some of these viruses can spread to humans, often causing severe disease and even death, such as coronavirus, Ebola virus and paramyxovirus. Even though they can host so many viruses, bats maintain a healthy state by producing only a limited inflammatory response. Uncovering the mechanisms by which bats fight off these viruses has important implications for human health. Aaron T. Irving's research team recently published an article in PNAS about the complementary mechanisms by which bats suppress inflammation.
Picture:Complementary relationship between M. davidii, E. spelaea, and P. alecto caspase-1 and IL-1β.(Published in PNAS)
Caspase-1(or cysteine aspartic protease 1)is the central inflammasome effector for pyroptosis and triggers cytokine ( such as IL-1β) secretion. The team identified residues in caspase-1 which are critical for enzymatic activity yet have been targeted for inhibition in Pteropus bats. Further, they discover cleavage-site flanking residues which led to the loss of IL-1β cleavage in Myotis bats. The team report an inverse relationship between caspase-1 function and IL-1β cleavage in bats within two suborders, with different evolutionary mechanisms resulting in a consistent reduction of downstream signaling by the inflammasome.
https://www.pnas.org/content/early/2020/10/21/2003352117
Dr Aaron Irving trained at the Diamantina Institute (UQ Australia), Monash Institute of Medical Research (Melbourne Australia) and Emerging Infectious Diseases, Duke-NUS Medial School (Singapore). He recently opened his lab at ZJE with a focus on emerging zoonotic viral infections and the host-pathogen interactions triggered by these viruses. There is a special interest in comparative biology using bats as a model organism and identifying key factors from bats that may be utilized to improve the human immune responses to pathogen infections. Other projects in the laboratory include novel diagnostic techniques to identify current or historical infection of wildlife by zoonotic viruses, including SARS-CoV-2, and establishing/evaluating factors that may contribute to zoonotic potential.