Constitutive TRIM22 Expression in the Respiratory Tract Confers a Pre-Existing Defence Against Influenza A Virus Infection

Matthew Charman, Steven McFarlane, Joanna K. Wojtus, Elizabeth Sloan, Rebecca Dewar, Gail Leeming, Mohammed Al-Saadi, Laura Hunter, Miles W. Carroll, James P. Stewart, Paul Digard, Edward Hutchinson*, Chris Boutell

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

The induction of antiviral effector proteins as part of a homeostatically controlled innate immune response to infection plays a critical role in limiting the propagation and transmission of respiratory pathogens. However, the prolonged induction of this immune response can lead to lung hyperinflammation, tissue damage, and respiratory failure. We hypothesized that tissues exposed to the constant threat of infection may constitutively express higher levels of antiviral effector proteins to reduce the need to activate potentially harmful innate immune defences. By analysing transcriptomic data derived from a range of human tissues, we identify lung tissue to express constitutively higher levels of antiviral effector genes relative to that of other mucosal and non-mucosal tissues. By using primary cell lines and the airways of rhesus macaques, we show the interferon-stimulated antiviral effector protein TRIM22 (TRIpartite Motif 22) to be constitutively expressed in the lung independently of viral infection or innate immune stimulation. These findings contrast with previous reports that have shown TRIM22 expression in laboratory-adapted cell lines to require interferon stimulation. We demonstrate that constitutive levels of TRIM22 are sufficient to inhibit the onset of human and avian influenza A virus (IAV) infection by restricting the onset of viral transcription independently of interferon-mediated innate immune defences. Thus, we identify TRIM22 to confer a pre-existing (intrinsic) intracellular defence against IAV infection in cells derived from the respiratory tract. Our data highlight the importance of tissue-specific and cell-type dependent patterns of pre-existing immune gene expression in the intracellular restriction of IAV from the outset of infection.

Original languageEnglish
Article number689707
Number of pages17
JournalFrontiers in Cellular and Infection Microbiology
Volume11
DOIs
Publication statusPublished - 21 Sep 2021

Bibliographical note

Funding Information: MCh, SM, and CB were funded by the UK Medical Research Council (MRC; MC_UU_12012/5 and MC_UU_12014/5) https://mrc.ukri.org/ awarded to CB. ES and EH were funded by the MRC (MR/N008618/1) awarded to EH. RD and PD were funded by the Biotechnology and Biological Sciences Research Council (BBSRC; BB/J004324 and BB/K012681/1) https:// bbsrc.ukri.org. MA-S and JS were funded by the BBSRC (BB/ K009664/1, BB/R00904X/1, and BB/R01863/1). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

We thank Professor Juergen Haas (University of Edinburgh) and Dr Benjamin Hale (University of Zurich), Professor Roger Everett (MRC-UoG CVR) for the provision of reagents, and Dr Seema Jasim (University of Edinburgh) for experimental assistance.

Open Access: This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Publisher Copyright: © Copyright © 2021 Charman, McFarlane, Wojtus, Sloan, Dewar, Leeming, Al-Saadi, Hunter, Carroll, Stewart, Digard, Hutchinson and Boutell.

Citation: Charman M, McFarlane S, Wojtus JK, Sloan E, Dewar R, Leeming G, Al-Saadi M, Hunter L, Carroll MW, Stewart JP, Digard P, Hutchinson E and Boutell C (2021) Constitutive TRIM22 Expression in the Respiratory Airway Confers a Pre-Existing Defence Against Influenza A Virus Infection. Front. Cell. Infect. Microbiol. 11:689707.

DOI: 10.3389/fcimb.2021.689707

Keywords

  • TRIM22
  • antiviral defence
  • influenza
  • intrinsic immunity
  • respiratory tract

Fingerprint

Dive into the research topics of 'Constitutive TRIM22 Expression in the Respiratory Tract Confers a Pre-Existing Defence Against Influenza A Virus Infection'. Together they form a unique fingerprint.

Cite this