Institut de Recherche en Infectiologie de Montpellier, CNRS, Université de Montpellier, CEDEX 5, 34293 Montpellier, France.
Centre International de Recherche en Infectiologie, INSERM/CNRS/UCBL1/ENS de Lyon, 69007 Lyon, France.
Viruses. 2021 Mar 22;13(3):522. doi: 10.3390/v13030522.
The threat of a new influenza pandemic is real. With past pandemics claiming millions of lives, finding new ways to combat this virus is essential. Host cells have developed a multi-modular system to detect incoming pathogens, a phenomenon called sensing. The signaling cascade triggered by sensing subsequently induces protection for themselves and their surrounding neighbors, termed interferon (IFN) response. This response induces the upregulation of hundreds of interferon-stimulated genes (ISGs), including antiviral effectors, establishing an antiviral state. As well as the antiviral proteins induced through the IFN system, cells also possess a so-called intrinsic immunity, constituted of antiviral proteins that are constitutively expressed, creating a first barrier preceding the induction of the interferon system. All these combined antiviral effectors inhibit the virus at various stages of the viral lifecycle, using a wide array of mechanisms. Here, we provide a review of mammalian and avian influenza A restriction factors, detailing their mechanism of action and in vivo relevance, when known. Understanding their mode of action might help pave the way for the development of new influenza treatments, which are absolutely required if we want to be prepared to face a new pandemic.
新流感大流行的威胁是真实存在的。过去的大流行导致数百万人死亡，因此寻找对抗这种病毒的新方法至关重要。宿主细胞已经开发出一种多模块系统来检测入侵的病原体，这种现象称为感应。感应引发的信号级联反应随后诱导自身和周围邻居的保护，称为干扰素（IFN）反应。这种反应诱导数百种干扰素刺激基因（ISGs）的上调，包括抗病毒效应物，从而建立抗病毒状态。除了通过 IFN 系统诱导的抗病毒蛋白外，细胞还具有所谓的固有免疫，由组成性表达的抗病毒蛋白组成，在诱导 IFN 系统之前形成第一道屏障。所有这些组合的抗病毒效应物在病毒生命周期的各个阶段抑制病毒，使用多种机制。在这里，我们综述了哺乳动物和禽源甲型流感的限制因子，详细说明了它们的作用机制及其在体内的相关性（如果已知的话）。了解它们的作用方式可能有助于为新的流感治疗方法铺平道路，如果我们要准备好应对新的大流行，这是绝对必要的。
