The Egyptian Rousette Genome Reveals Unexpected Features of Bat Antiviral Immunity

Bats harbor many viruses asymptomatically, including several notorious for causing extreme virulence in humans. To identify differences between antiviral mechanisms in humans and bats, we sequenced, assembled, and analyzed the genome of Rousettus aegyptiacus, a natural reservoir of Marburg virus and the only known reservoir for any filovirus. We found an expanded and diversified KLRC/KLRD family of natural killer cell receptors, MHC class I genes, and type I interferons, which dramatically differ from their functional counterparts in other mammals. Such concerted evolution of key components of bat immunity is strongly suggestive of novel modes of antiviral defense. An evaluation of the theoretical function of these genes suggests that an inhibitory immune state may exist in bats. Based on our findings, we hypothesize that tolerance of viral infection, rather than enhanced potency of antiviral defenses, may be a key mechanism by which bats asymptomatically host viruses that are pathogenic in humans. [Display omitted] •High-contiguity genome assembly for Rousettus aegyptiacus, a host of Marburg virus•Expansion of NK cell receptors, MHC class I genes, and type I interferons•Genetic signatures of unique signaling in NK cell receptors in multiple bats•Enhanced infection tolerance may be an antiviral defense strategy in bats The genome of the Egyptian fruit bat reveals how its immune defenses allow tolerance of pathogenic viruses.