Constitutive IFNα Protein Production in Bats

Abstract

Bats are the only mammals with self-powered flight and account for 20% of all extant mammalian diversity. In addition, they harbor many emerging and reemerging viruses, including multiple coronaviruses, several of which are highly pathogenic in other mammals, but cause no disease in bats. How this symbiotic relationship between bats and viruses exists is not yet fully understood. Existing evidence supports a specific role for the innate immune system, in particular type I interferon (IFN) responses, a major component of antiviral immunity. Previous studies in bats have shown that components of the IFN pathway are constitutively activated at the transcriptional level. In this study, we tested the hypothesis that the type I IFN response in bats is also constitutively activated at the protein level. For this, we utilized highly sensitive Single Molecule (Simoa) digital ELISA assays, previously developed for humans that we adapted to bat samples. We prospectively sampled four non-native chiroptera species from French zoos. We identified a constitutive expression of IFNα protein in the circulation of healthy bats, and concentrations that are physiologically active in humans. Expression levels differed according to the species examined, but were not associated with age, sex, or health status suggesting constitutive IFNα protein expression independent of disease. These results confirm a unique IFN response in bat species that may explain their ability to coexist with multiple viruses in the absence of pathology. These results may help to manage potential zoonotic viral reservoirs and potentially identify new anti-viral strategies.

Transcriptional dynamics of transposable elements in the type I IFN response in Myotis lucifugus cells

“…Finally, our observations may reflect a unique attribute of bat immunity, consistent with the idea that some bat species exhibit constitutive IFN expression [ 7 , 57 ]. Although the type I IFN locus of M. lucifugus is poorly characterized, we were able to annotate at least 11 uncharacterized genes that likely reflect the expansion by gene duplication of the IFNw cluster (Fig.…”

Transcriptional dynamics of transposable elements in the type I IFN response in Myotis lucifugus cells

“…Finally, our observations may reflect a unique attribute of bat immunity, consistent with the idea that some bat species exhibit constitutive IFN expression [7, 55]. Although the type I IFN locus of M. lucifugus is poorly characterized, we were able to annotate at least 11 uncharacterized genes that likely reflect the expansion by gene duplication of the IFNw cluster (Fig.…”

Species-Specific Molecular Barriers to SARS-CoV-2 Replication in Bat Cells

“…This inability to evade the expression of two ISGs in E. serotinus kidney cells and in Myotis myotis nasal epithelial cells may contribute to the cellular control of infection in these cells, as in experimentally infected E. fuscus ( 66 ). Alternatively, the basal level of IFN may be high in these two cell lines, as reported in several other bat species ( 67 – 69 ). Expression of a mutated form of IRF3, which is a key transcription factor involved in the induction of the IFN signaling cascade, contributes to enhanced IFN responses in bat species, including E. fuscus , compared to humans ( 70 ).…”