No abstract

Compared with terrestrial mammals, bats have a longer lifespan and greater capacity to co-exist with a variety of viruses. In addition to cytosolic DNA generated by these viral infections, the metabolic demands of flight cause DNA damage and the release of self-DNA into the cytoplasm. However, whether bats have an altered DNA sensing/defense system to balance high cytosolic DNA levels remains an open question. We demonstrate that bats have a dampened interferon response due to the replacement of the highly conserved serine residue (S358) in STING, an essential adaptor protein in multiple DNA sensing pathways. Reversing this mutation by introducing S358 restored STING functionality, resulting in interferon activation and virus inhibition. Combined with previous reports on bat-specific changes of other DNA sensors such as TLR9, IFI16, and AIM2, our findings shed light on bat adaptation to flight, their long lifespan, and their unique capacity to serve as a virus reservoir.

Bats have emerged as unique mammalian vectors harboring a diverse range of highly lethal zoonotic viruses with minimal clinical disease. Despite having sustained complete genomic loss of AIM2, regulation of the downstream inflammasome response in bats is unknown. AIM2 sensing of cytoplasmic DNA triggers ASC aggregation and recruits caspase-1, the central inflammasome effector enzyme, triggering cleavage of cytokines such as IL-1β and inducing GSDMD-mediated pyroptotic cell death. Restoration of AIM2 in bat cells led to intact ASC speck formation, but intriguingly resulted in a lack of caspase-1 or consequent IL-1β activation. We further identified two residues undergoing positive selection pressures in Pteropus alecto caspase-1 that abrogate its enzymatic function and are crucial in human caspase-1 activity. Functional analysis of another bat lineage revealed a targeted mechanism for loss of Myotis davidii IL-1β cleavage and elucidated an inverse complementary relationship between caspase-1 and IL-1β, resulting in overall diminished signaling across bats of both suborders. Thus we report strategies that additionally undermine downstream inflammasome signaling in bats, limiting an overactive immune response against pathogens while potentially producing an antiinflammatory state resistant to diseases such as atherosclerosis, aging, and neurodegeneration.

When preparing for the coronavirus disease 2019 pandemic and its effects on the CNS, radiologists should be familiar with neuroimaging appearances in past zoonotic infectious disease outbreaks. Organisms that have crossed the species barrier from animals to humans include viruses such as Hendra, Nipah, Severe Acute Respiratory Syndrome, and influenza, as well as bacteria and others. Brain CT and MR imaging findings have included cortical abnormalities, microinfarction in the white matter, largevessel occlusion, and features of meningitis. In particular, the high sensitivity of diffusion-weighted MR imaging in detecting intracranial abnormalities has been helpful in outbreaks. Although the coronaviruses causing the previous Severe Acute Respiratory Syndrome outbreak and the current coronavirus disease 19 pandemic are related, it is important to be aware of their similarities as well as potential differences. This review describes the neuroimaging appearances of selected zoonotic outbreaks so that neuroradiologists can better understand the current pandemic and potential future outbreaks.