The Egyptian Rousette Genome Reveals Unexpected Features of Bat Antiviral Immunity

Cell. 2018 May 17;173(5):1098-1110.e18. doi: 10.1016/j.cell.2018.03.070. Epub 2018 Apr 26.

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.

Keywords: Chiroptera; antiviral immunity; filovirus; genome; innate immunity; natural killer cell receptors; type I interferon.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Chiroptera / classification
  • Chiroptera / genetics*
  • Chiroptera / immunology
  • Chromosome Mapping
  • Disease Reservoirs / virology
  • Egypt
  • Evolution, Molecular
  • Genetic Variation
  • Genome*
  • Histocompatibility Antigens Class I / classification
  • Histocompatibility Antigens Class I / genetics
  • Humans
  • Immunity, Innate / genetics*
  • Interferon Type I / classification
  • Interferon Type I / genetics
  • Marburg Virus Disease / immunology
  • Marburg Virus Disease / pathology
  • Marburgvirus / physiology
  • NK Cell Lectin-Like Receptor Subfamily C / chemistry
  • NK Cell Lectin-Like Receptor Subfamily C / classification
  • NK Cell Lectin-Like Receptor Subfamily C / genetics
  • NK Cell Lectin-Like Receptor Subfamily D / chemistry
  • NK Cell Lectin-Like Receptor Subfamily D / classification
  • NK Cell Lectin-Like Receptor Subfamily D / genetics
  • Phylogeny
  • Sequence Alignment

Substances

  • Histocompatibility Antigens Class I
  • Interferon Type I
  • NK Cell Lectin-Like Receptor Subfamily C
  • NK Cell Lectin-Like Receptor Subfamily D