Constitutive TRIM22 expression in the respiratory airway confers a pre-existing defence against influenza A virus infection

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

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
JournalFrontiers in Cellular and Infection Microbiology
Early online date21 Sep 2021
DOIs
Publication statusE-pub ahead of print - 21 Sep 2021

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