Dampened STING-Dependent Interferon Activation in Bats

Cell Host Microbe. 2018 Mar 14;23(3):297-301.e4. doi: 10.1016/j.chom.2018.01.006. Epub 2018 Feb 22.


Compared with terrestrial mammals, bats have a longer lifespan and greater capacity to co-exist with a variety of viruses. In addition to cytosolic DNA generated by these viral infections, the metabolic demands of flight cause DNA damage and the release of self-DNA into the cytoplasm. However, whether bats have an altered DNA sensing/defense system to balance high cytosolic DNA levels remains an open question. We demonstrate that bats have a dampened interferon response due to the replacement of the highly conserved serine residue (S358) in STING, an essential adaptor protein in multiple DNA sensing pathways. Reversing this mutation by introducing S358 restored STING functionality, resulting in interferon activation and virus inhibition. Combined with previous reports on bat-specific changes of other DNA sensors such as TLR9, IFI16, and AIM2, our findings shed light on bat adaptation to flight, their long lifespan, and their unique capacity to serve as a virus reservoir.

Keywords: DNA sensing; STING; bats; dampened; interferon; virus.

MeSH terms

  • Animals
  • Cell Line
  • Chiroptera / genetics
  • Chiroptera / immunology*
  • Chiroptera / virology*
  • Cytoplasm / virology
  • Cytosol / metabolism
  • DNA Damage
  • DNA, Viral / metabolism
  • DNA-Binding Proteins
  • Disease Reservoirs
  • Gene Expression
  • HEK293 Cells
  • Humans
  • Interferons / metabolism*
  • Membrane Proteins / genetics
  • Membrane Proteins / immunology*
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mutation
  • Nuclear Proteins / metabolism
  • Phosphoproteins / metabolism
  • Sendai virus
  • Sequence Analysis, RNA
  • Toll-Like Receptor 9 / immunology
  • Virus Diseases / immunology*
  • Virus Diseases / veterinary*


  • DNA, Viral
  • DNA-Binding Proteins
  • Membrane Proteins
  • Nuclear Proteins
  • Phosphoproteins
  • STING1 protein, human
  • Sting1 protein, mouse
  • Toll-Like Receptor 9
  • Interferons