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.

TRIM14 是先天免疫的重要组成部分，可保护生物体免受各种病毒的侵害。结果表明，TRIM14 以不依赖干扰素的方式限制细胞培养物中的甲型流感病毒 (IAV) 感染。然而，尚不清楚 TRIM14 是否影响 IAV 体内 IAV 感染后的繁殖和免疫系统反应。为了研究 TRIM14 在有机体水平上的作用，我们生成了过表达人TRIM14的转基因小鼠基因。我们发现 IAV 繁殖在转基因小鼠的肺部受到强烈抑制，导致转基因动物的存活率增加。引人注目的是，在 IAV 感染后，编码干扰素、IL-6、IL-1β 和 TNFα 的基因转录在转基因动物的肺中明显弱于对照小鼠，因此表明不存在干扰素和炎症反应的显着诱导。在TRIM14被意外下调的转基因小鼠脾脏中，在 IAV 感染后，编码干扰素的基因转录反而增加。因此，我们证明了 TRIM14 在模型生物体的抗 IAV 保护中的关键作用，这种作用是在没有明显激活其他先天免疫系统途径的情况下实现的。