Unconventional IFNω-like genes dominate the type I IFN locus and the constitutive antiviral responses in bats

Abstract

Bats are the natural reservoir hosts of some viruses, some of which may spillover to humans and cause global-scale pandemics. Different to humans, bats may coexist with high pathogenic viruses without showing symptoms of diseases. As one of the most important first defenses, bat type I interferon (IFN-Is) were thought to play a role during this virus coexistence and thus were studied in recent years. However, there are arguments that whether bats have a contracted genome locus or constitutive expressed IFNs, mainly due to species-specific findings. We hypothesized that because of the lacking of pan-bat analysis, the common characters for bat IFN-Is have not been revealed yet. Here, we characterized the IFN-I locus for 9 Yangochiroptera bats and 3 Yinpterochiroptera based on the their high quality bat genomes. We also compared the basal expression for 6 bats and compared the antiviral, anti-proliferative activity and thermo-stability of a representative Rhinolophus bat IFNs. We found a dominance of unconventional IFN{omega}-like responses in the IFN-I system, which is unique to bats. In contrast to IFNa-dominated IFN-I loci in the majority of other mammals, bats generally have shorter IFN-I loci with more unconventional IFN{omega}-like genes (IFN{omega} or related IFNa{omega}), but with less or even no IFNa genes. In addition, bats generally have constitutively expressed IFNs, the highest expressed of which is more likely an IFN{omega}-like gene. Likewise, the highly expressed IFN{omega}-like protein also demonstrated the best antiviral activity, anti-proliferative activity or thermo-stability, as shown in a representative Rhinolophus bat species. Overall, we revealed pan-bat unique characteristics in IFN-I system, which provide insights into our understanding of the innate immunity that contribute to a special coexistence between bats and viruses.