Why do bats excel as viral reservoirs and don’t get sick?


Bats act as reservoirs for numerous zoonotic viruses, including SARS-CoV, MERS CoV, Ebola virus, and most likely SARS-CoV-2, the pathogen behind the ongoing coronavirus pandemic. However, the molecular mechanisms that bats use to tolerate pathogenic viruses have remained unclear.

Now scientists at Duke-NUS Medical School, Singapore, have discovered new molecular mechanisms that allow bats to tolerate zoonotic viruses without getting sick. Published this week in the Proceedings of the National Academy of Sciences (PNAS), the study suggests that bats adopt unique strategies to prevent overactive immune responses, which protect them from diseases caused by zoonotic viruses.

The team examined three bat species – Pteropus alecto (black fruit bat), Eonycteris spelaea (cave nectar bat) and Myotis davidii (David’s myotid bat) – and identified mechanisms that balance the activity of key proteins. which play an important role in mediating immunity and inflammatory responses in mammals. These mechanisms allow bats to host and transmit zoonotic pathogens without triggering the harmful consequences of immune activation.

One of the mechanisms used by bats is to reduce the levels of caspase-1, a protein that triggers a key inflammatory cytokine protein, interleukin-1 beta (IL-1β). Another mechanism they employ hinders the maturation of interleukin-1 beta cytokines through a finely tuned balance between caspase-1 and IL-1β.

“Suppression of overactive inflammatory responses improves longevity and prevents age-related decline in humans. Our findings may offer potential insights for the development of novel therapeutic strategies capable of controlling and treating human infectious diseases, “said Professor Wang Linfa, senior author and correspondent of the study in Duke’s Emerging Infectious Diseases (EID) program. NUS.

“This study exemplifies world-class research led by our talented faculty to advance fundamental scientific knowledge. Professor Wang’s research is all the more important in the context of COVID-19, contributing to a greater understanding of how zoonotic diseases persist. in the wild, and potentially helping new approaches to managing future outbreaks, ”said Professor Patrick Casey, senior vice president of research, Duke-NUS Medical School.

Goh G, Ahn M, Zhu F, et al. Complementary regulation of caspase-1 and IL-1β reveals additional mechanisms of attenuated inflammation in bats. PNAS. Published online 22 October 2020. doi: 10.1073 / pnas.2003352117

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