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Human TRIM14 protects transgenic mice from influenza A viral infection without activation of other innate immunity pathways

Genes & Immunity volume 22, pages 56–63 (2021)Cite this article

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Abstract

TRIM14 is an important component of innate immunity that defends organism from various viruses. It was shown that TRIM14 restricted influenza A virus (IAV) infection in cell cultures in an interferon-independent manner. However, it remained unclear whether TRIM14 affects IAV reproduction and immune system responses upon IAV infection in vivo. In order to investigate the effects of TRIM14 at the organismal level we generated transgenic mice overexpressing human TRIM14 gene. We found that IAV reproduction was strongly inhibited in lungs of transgenic mice, resulting in the increased survival of transgenic animals. Strikingly, upon IAV infection, the transcription of genes encoding interferons, IL-6, IL-1β, and TNFα was notably weaker in lungs of transgenic animals than that in control mice, thus indicating the absence of significant induction of interferon and inflammatory responses. In spleen of transgenic mice, where TRIM14 was unexpectedly downregulated, upon IAV infection the transcription of genes encoding interferons was oppositely increased. Therefore, we demonstrated the key role of TRIM14 in anti-IAV protection in the model organism that is realized without noticeable activation of other innate immune system pathways.

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Fig. 1: The influence of TRIM14 on IAV infection in transgenic mice lines Tg1 and Tg4.
Fig. 2: TRIM14 transcription level is increased in lung and decreased in spleen of transgenic mice.
Fig. 3: IFN response is not induced in the lung of transgenic mice upon IAV infection.
Fig. 4: IFN response is enhanced in the spleen of transgenic mice after 24 h of IAV infection.
Fig. 5: Pro-inflammatory response is partially inhibited in the lung of transgenic mice upon IAV infection.
Fig. 6: A proposed model of the influence of TRIM14 overexpression on the immune gene transcription upon IAV infection.

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Acknowledgements

This work was supported by the Russian Foundation for Basic Research (grant numbers 18–04–00733, 18–34–00484, and 20–015–00272) and Russian Fundamental Scientific Research Program (АААА-А19-119022290059-8).

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  1. These authors contributed equally: Valentina V. Nenasheva, Natalia A. Nikitenko

Authors and Affiliations

  1. Department of Viral and Cellular Molecular Genetics, Institute of Molecular Genetics of National Research Centre “Kurchatov Institute”, Moscow, Russia

    Valentina V. Nenasheva, Ekaterina A. Stepanenko, Irina V. Makarova, Lyudmila E. Andreeva, Galina V. Kovaleva & Vyacheslav Z. Tarantul

  2. Department of Medical Microbiology, N. F. Gamaleya National Research Centre of Epidemiology and Microbiology, Moscow, Russia

    Natalia A. Nikitenko, Andrey A. Lysenko, Amir I. Tukhvatulin & Denis Y. Logunov

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Nenasheva, V.V., Nikitenko, N.A., Stepanenko, E.A. et al. Human TRIM14 protects transgenic mice from influenza A viral infection without activation of other innate immunity pathways. Genes Immun 22, 56–63 (2021). https://doi.org/10.1038/s41435-021-00128-6

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