Bats host a large number of zoonotic viruses, including several viruses that are highly pathogenic to other mammals. The mechanisms underlying this rich viral diversity are unknown, but they may be linked to unique immunological features that allow bats to act as asymptomatic viral reservoirs. Vertebrates respond to viral infection by inducing IFNs, which trigger antiviral defenses through IFN-stimulated gene (ISG) expression. Although the IFN system of several bats is characterized at the genomic level, less is known about bat IFN-mediated transcriptional responses. In this article, we show that IFN signaling in bat cells from the black flying fox (Pteropus alecto) consists of conserved and unique ISG expression profiles. In IFN-stimulated cells, bat ISGs comprise two unique temporal subclusters with similar early induction kinetics but distinct late-phase declines. In contrast, human ISGs lack this decline phase and remained elevated for longer periods. Notably, in unstimulated cells, bat ISGs were expressed more highly than their human counterparts. We also found that the antiviral effector 2-5A–dependent endoribonuclease, which is not an ISG in humans, is highly IFN inducible in black flying fox cells and contributes to cell-intrinsic control of viral infection. These studies reveal distinctive innate immune features that may underlie a unique virus–host relationship in bats.
This work was supported in part by National Institutes of Health Grant AI117922 (to J.W.S.), the University of Texas Southwestern Endowed Scholars Program (to J.W.S.), the University of Texas Southwestern High Impact/High Risk Grant Program (to J.W.S.), the William F. and Grace H. Kirkpatrick Award (to P.C.D.L.C.-R.), and National Research Foundation-Competitive Research Programme Grant NRF2012NRF-CRP001–056 (to L.-F.W.). C.X. was partially supported by National Institutes of Health Grant UL1TR001105.
The sequences presented in this article have been submitted to the Gene Expression Omnibus (https://www.ncbi.nlm.nih.gov/geo/) under accession number GSE102296.
The online version of this article contains supplemental material.
Abbreviations used in this article:
- clustered regularly interspaced short palindromic repeats
- fold change
- false discovery rate
- IFN-stimulated gene
- nonessential amino acids
- oligoadenylate synthase
- polyinosinic-polycytidylic acid
- 2-5A–dependent endoribonuclease
- RNA sequencing
- vesicular stomatitis virus
- yellow fever virus.
- Received August 24, 2017.
- Accepted October 25, 2017.
- Copyright © 2017 by The American Association of Immunologists, Inc.