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

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 hyperinflamm...

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Autores principales: Charman, Matthew, McFarlane, Steven, Wojtus, Joanna K., Sloan, Elizabeth, Dewar, Rebecca, Leeming, Gail, Al-Saadi, Mohammed, Hunter, Laura, Carroll, Miles W., Stewart, James P., Digard, Paul, Hutchinson, Edward, Boutell, Chris
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8490869/
https://www.ncbi.nlm.nih.gov/pubmed/34621686
http://dx.doi.org/10.3389/fcimb.2021.689707
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author Charman, Matthew
McFarlane, Steven
Wojtus, Joanna K.
Sloan, Elizabeth
Dewar, Rebecca
Leeming, Gail
Al-Saadi, Mohammed
Hunter, Laura
Carroll, Miles W.
Stewart, James P.
Digard, Paul
Hutchinson, Edward
Boutell, Chris
author_facet Charman, Matthew
McFarlane, Steven
Wojtus, Joanna K.
Sloan, Elizabeth
Dewar, Rebecca
Leeming, Gail
Al-Saadi, Mohammed
Hunter, Laura
Carroll, Miles W.
Stewart, James P.
Digard, Paul
Hutchinson, Edward
Boutell, Chris
author_sort Charman, Matthew
collection PubMed
description 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.
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spelling pubmed-84908692021-10-06 Constitutive TRIM22 Expression in the Respiratory Tract Confers a Pre-Existing Defence Against Influenza A Virus Infection Charman, Matthew McFarlane, Steven Wojtus, Joanna K. Sloan, Elizabeth Dewar, Rebecca Leeming, Gail Al-Saadi, Mohammed Hunter, Laura Carroll, Miles W. Stewart, James P. Digard, Paul Hutchinson, Edward Boutell, Chris Front Cell Infect Microbiol Cellular and Infection Microbiology 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. Frontiers Media S.A. 2021-09-21 /pmc/articles/PMC8490869/ /pubmed/34621686 http://dx.doi.org/10.3389/fcimb.2021.689707 Text en Copyright © 2021 Charman, McFarlane, Wojtus, Sloan, Dewar, Leeming, Al-Saadi, Hunter, Carroll, Stewart, Digard, Hutchinson and Boutell https://creativecommons.org/licenses/by/4.0/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.
spellingShingle Cellular and Infection Microbiology
Charman, Matthew
McFarlane, Steven
Wojtus, Joanna K.
Sloan, Elizabeth
Dewar, Rebecca
Leeming, Gail
Al-Saadi, Mohammed
Hunter, Laura
Carroll, Miles W.
Stewart, James P.
Digard, Paul
Hutchinson, Edward
Boutell, Chris
Constitutive TRIM22 Expression in the Respiratory Tract Confers a Pre-Existing Defence Against Influenza A Virus Infection
title Constitutive TRIM22 Expression in the Respiratory Tract Confers a Pre-Existing Defence Against Influenza A Virus Infection
title_full Constitutive TRIM22 Expression in the Respiratory Tract Confers a Pre-Existing Defence Against Influenza A Virus Infection
title_fullStr Constitutive TRIM22 Expression in the Respiratory Tract Confers a Pre-Existing Defence Against Influenza A Virus Infection
title_full_unstemmed Constitutive TRIM22 Expression in the Respiratory Tract Confers a Pre-Existing Defence Against Influenza A Virus Infection
title_short Constitutive TRIM22 Expression in the Respiratory Tract Confers a Pre-Existing Defence Against Influenza A Virus Infection
title_sort constitutive trim22 expression in the respiratory tract confers a pre-existing defence against influenza a virus infection
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8490869/
https://www.ncbi.nlm.nih.gov/pubmed/34621686
http://dx.doi.org/10.3389/fcimb.2021.689707
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