Ancient and modern coevolution between bat immunity and viruses – BATantiVIR

To address this, we have built a strong collaboration to combine (phylo)genetics, eco-epidemiology and functional approaches, notably including unique bat and circulating virus sampling, novel genomic/transcriptomic data, new (phylo)genetic methods, and cutting-edge mechanistic virus-host studies that will include new bat cells.

Here, we have characterized the functional diversification of the Protein kinase R (PKR), a major antiviral innate defense system. Our data indicate that PKR has evolved under positive selection and has undergone repeated genomic duplications in bats, in contrast to all studied mammals that possess a single copy of the gene. Functional testing of the relationship between PKR and poxvirus antagonists revealed how an evolutionary conflict with ancient pathogenic poxviruses has shaped a specific bat host-virus interface. More importantly, we determined that duplicated PKRs of the Myotis species have undergone functional diversification allowing them to collectively escape from and enhance control of DNA and RNA viruses. These findings suggest that viral-driven adaptations in PKR contribute to modern virus-bat interactions and may account for bat specific immunity.

This will bring important insights on unique antiviral defenses, impact of viruses on bat populations, as well as on genetic determinants of host species specificity, which partly contribute to current and future epidemics.

www.biorxiv.org/content/10.1101/2022.06.28.497829v1
www.biorxiv.org/content/10.1101/2022.04.07.487460v1

Bats harbour a high number of viruses, but appear asymptomatic to most viral infections that are pathogenic to other mammals. It seems that they have evolved a unique balance between immune resistance and viral tolerance. However, most of bat immune evolutionary and functional history remains unknown. Here, we aim to decipher how bat’s immunity has adapted to long-term association with diverse viruses and to determine whether modern viruses induce a fitness cost on bats. Specifically, we will characterize the evolutionary and functional diversification of a major antiviral effector in bats, in which we found rapid and unique functional adaptations at the molecular and genomic level. To address this, we have built a strong collaboration to combine (phylo)genetics and functional approaches, notably including unique bat and circulating virus sampling, novel genomic/transcriptomic data, new (phylo)genetic methods, and cutting-edge mechanistic virus-host studies that will include CRISPR/Cas KO/KI bat cells. This will bring important insights on unique antiviral defences, impact of viruses on bat populations, as well as on genetic determinants of host species specificity, which partly contribute to current and future epidemics.