Contraction of the type I IFN locus and unusual constitutive expression of IFN-α in bats
- aAustralian Animal Health Laboratory, Health and Biosecurity Business Unit, Commonwealth Scientific and Industrial Research Organisation, Geelong, Victoria 3220, Australia;
- bProgram in Emerging Infectious Diseases, Duke–National University of Singapore Medical School, Singapore 169857;
- cAustralian Animal Health Laboratory, Commonwealth Scientific and Industrial Research Organisation, Geelong, Victoria 3220, Australia;
- dCentre for Biomedical Research, Burnet Institute, Melbourne, Victoria 3004, Australia;
- eDepartment of Microbiology, Monash University, Clayton, Victoria 3168, Australia;
- fDepartment of Infectious Diseases, Monash University, Melbourne, Victoria 3004, Australia;
- gDepartment of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, Victoria 3010, Australia
See allHide authors and affiliations
Edited by George R. Stark, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, OH, and approved January 26, 2016 (received for review September 22, 2015)

Significance
Here we provide what is, to our knowledge, the first gene map of the type I IFN region of any bat species with the sequence of the type I IFN locus of the Australian black flying fox, Pteropus alecto. The bat IFN locus contains fewer IFN genes compared with any other mammal sequenced to date, including only three IFN-α genes. We also demonstrate that bat IFN-α genes are constitutively expressed in unstimulated bat tissues and cells and that their expression is unaffected by viral infection. This unusual pattern of IFN-α expression has not been described in any other species to our knowledge and has important implications for the role of innate immunity in the ability of bats to coexist with viruses in the absence of disease.
Abstract
Bats harbor many emerging and reemerging viruses, several of which are highly pathogenic in other mammals but cause no clinical signs of disease in bats. To determine the role of interferons (IFNs) in the ability of bats to coexist with viruses, we sequenced the type I IFN locus of the Australian black flying fox, Pteropus alecto, providing what is, to our knowledge, the first gene map of the IFN region of any bat species. Our results reveal a highly contracted type I IFN family consisting of only 10 IFNs, including three functional IFN-α loci. Furthermore, the three IFN-α genes are constitutively expressed in unstimulated bat tissues and cells and their expression is unaffected by viral infection. Constitutively expressed IFN-α results in the induction of a subset of IFN-stimulated genes associated with antiviral activity and resistance to DNA damage, providing evidence for a unique IFN system that may be linked to the ability of bats to coexist with viruses.
Footnotes
- ↵1To whom correspondence may be addressed. Email: peng.zhou{at}duke-nus.edu.sg or michelle.baker{at}csiro.au.
Author contributions: P.Z., M.T., L.-F.W., and M.L.B. designed research; P.Z., M.T., V.B., I.S., J.H.J.N., L.M., and M.L.B. performed research; W.P.M. and I.H.M. contributed new reagents/analytic tools; P.Z., M.T., J.W.W., J.C., C.C., J.H.J.N., L.M., G.T., and M.L.B. analyzed data; and P.Z., M.T., G.T., and M.L.B. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
Data deposition: Nucleotide sequence data have been deposited in the GenBank database [accession nos. KT384435–KT384439 (bat BAC clones 19–21) and KT384440 (cloned 3-kb bat IFN region)]. RNA sequence data have been deposited in the Sequence Read Archive [accession nos. SRP067312 (uninfected HEK293T cells) and SRP067371 (PaKiT03 cells)].
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1518240113/-/DCSupplemental.
Citation Manager Formats
Article Classifications
- Biological Sciences
- Immunology and Inflammation