Genomic analysis and examination of innate antiviral immunity in the Egyptian rousett bat
Pavlovich, Stephanie Sarah
MetadataShow full item record
Bats asymptomatically host a number of viruses that are the cause of recently emergent infectious diseases in humans. While the mechanisms underlying this asymptomatic infection are currently not known, studies of sequenced bat genomes help uncover genetic adaptations in bats that may have functional importance in the antiviral response of these animals. To identify differences between antiviral mechanisms in humans and bats, we sequenced, assembled, and analyzed the genome of the Egyptian rousette bat (ERB; Rousettus aegyptiacus), a natural reservoir of Marburg virus and the only known reservoir for any filovirus. We used this genome to understand the evolution of immune genes and gene families in bats, and describe several observations relevant to defense against viruses. We observed an unusual expansion of the NKG2/CD94 natural killer (NK) cell receptor gene families in Egyptian rousette bats relative to other species, and found genomic evidence of unique features and expression of these receptors that may result in a net inhibitory balance within bat NK cells. The expansion of NK cell receptors is matched by an expansion of potential major histocompatibility complex (MHC) class I ligands, which are distributed both within and, surprisingly, outside the canonical MHC loci. We also observed that the type I interferon (IFN) locus is considerably expanded and diversified in the ERB, and that the IFN-ω subfamily contributes most to this expansion. To understand the functional implications of this expansion, we synthesized multiple IFN-ω proteins and examined their antiviral effects. Members of this subfamily are not constitutively expressed but are induced after viral infection, and show antiviral activity in vitro, with different antiviral potencies observed for different IFN-ω proteins. Taken together, these results show that multiple bats, including the ERB, have expanded and diversified numerous antiviral loci, and potentially developed unique adaptations in NK cell receptor signaling, and type I IFN responses. The concerted evolution of so many key components of immunity in the ERB is strongly suggestive of novel modes of antiviral defense that may contribute to the ability of bats to asymptomatically host viruses that are pathogenic in humans.