The Egyptian Rousette Genome Reveals Unexpected Features of Bat Antiviral Immunity

Abstract

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.

Origin and evolution of the major histocompatibility complex class I region in eutherian mammals

“…Therefore, although possible chimeras and/or artifacts in these genome assemblies cannot be completely ruled out, we believe that if any occurred, they would not influence the overall results and conclusions of this study. Indeed, our results from two bats are in agreement with previous studies (Ng et al, ; Pavlovich et al, ). Since the MHCI regions in these species are fragmented to some degree, chromosome‐level genome sequences obtained by a combination of multiple sequencing methods will help confirm our observations.…”

“…In this study, we investigated MHCI gene content and organization in the genomes of wild species. Consistent with the findings of Ng et al () and Pavlovich et al (), we found for all four bat species, that within the canonical MHCI region (CMR), only the β block contained one to several MHCI genes, whereas most MHCI genes were apparently outside the CMR (Figure ). Intriguingly, uniquely in the common vampire bat, 11 of 18 genes were detected flanking one another on a scaffold not in the CMR (Figure ), suggesting that a regional duplication has occurred.…”

“…In agreement with the results of Ng et al (), in all four bat species examined in this study representing both suborders of Chiroptera, we found the α1 antigen‐binding domain in MHCI genes to be three or five amino acids (AAs) longer than in the other eutherian mammals (Figure and Figure ), suggesting that this is a common feature across bats. Pavlovich et al () showed that MHCI genes with an additional three AAs were transcribed in almost all bat tissues. Most importantly, Wynne et al () demonstrated that functional MHCI allele Ptal‐N*01:01 in the black flying fox has a three‐AA insertion in the same position, that its product can present virus‐derived peptides on the cell surface, and that the peptides presented show a broader length distribution than those presented by MHCIs in other mammals.…”

Holy Immune Tolerance, Batman!

“…How bats cope with such pathogens remains elusive. In a recent issue of Cell, Pavlovich et al (2018) describe several key adaptations in innate immune-related genes that suggest that the Egyptian rousette fruit bat relies on immune tolerance mechanisms to manage viral infections.…”

“…A recent study from Pavlovich et al proposes a mechanism of disease tolerance to explain why the Egyptian rousette fruit bat (Rousettus aegyptiacus), a natural host of the Marburg virus, is able to asymptomatically harbor a pathogen known to devastate humans (Pavlovich et al, 2018). The authors utilize a comparative immunogenomic approach to gain insight into the evolution of gene families involved in innate immune responses and antiviral defense in R. aegyptiacus.…”