IRF7 in the Australian black flying fox, Pteropus alecto: evidence for a unique expression pattern and functional conservation

PLoS One. 2014 Aug 6;9(8):e103875. doi: 10.1371/journal.pone.0103875. eCollection 2014.

Abstract

As the only flying mammal, bats harbor a number of emerging and re-emerging viruses, many of which cause severe diseases in humans and other mammals yet result in no clinical symptoms in bats. As the master regulator of the interferon (IFN)-dependent immune response, IFN regulatory factor 7 (IRF7) plays a central role in innate antiviral immunity. To explore the role of bat IRF7 in the regulation of the IFN response, we performed sequence and functional analysis of IRF7 from the pteropid bat, Pteropus alecto. Our results demonstrate that bat IRF7 retains the ability to bind to MyD88 and activate the IFN response despite unique changes in the MyD88 binding domain. We also demonstrate that bat IRF7 has a unique expression pattern across both immune and non-immune related tissues and is inducible by double-strand RNA. The broad tissue distribution of IRF7 may provide bats with an enhanced ability to rapidly activate the IFN response in a wider range of tissues compared to other mammals. The importance of IRF7 in antiviral activity against the bat reovirus, Pulau virus was confirmed by siRNA knockdown of IRF7 in bat cells resulting in enhanced viral replication. Our results highlight the importance of IRF7 in innate antiviral immunity in bats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Chiroptera / genetics
  • Chiroptera / immunology
  • Chiroptera / metabolism*
  • Gene Expression Regulation / physiology*
  • Immunity, Innate / physiology
  • Interferon Regulatory Factor-7 / biosynthesis*
  • Interferon Regulatory Factor-7 / genetics
  • Interferon Regulatory Factor-7 / immunology
  • Molecular Sequence Data
  • Myeloid Differentiation Factor 88 / genetics
  • Myeloid Differentiation Factor 88 / immunology
  • Myeloid Differentiation Factor 88 / metabolism*
  • Organ Specificity / physiology

Substances

  • Interferon Regulatory Factor-7
  • Myeloid Differentiation Factor 88

Associated data

  • GENBANK/KJ534586

Grants and funding

This work was supported by funding from the Australian Research Council Future Fellowship (FT110100234) to M. L. B. and a CSIRO OCE Science Leaders award to L. -F. W. and support from the Victorian Government’s Operational Infrastructure Support Program. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.