Mammalian and Avian Host Cell Influenza A Restriction Factors

Abstract

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.

Keywords: influenza virus; innate immunity; interferon; restriction factors.

Figure 1

Annotated schematic representation of an IAV virion.

Figure 2

Schematic representation of IAV sensing and subsequent IFN signaling.

Figure 3

Schematic representation of IAV life cycle with the host cell restriction factors that target each step. Factors highlighted in green are those that are generally accepted or that have consequent data backing them, in orange factors that need further investigation to confirm their role as IAV restriction factors for instance in vivo (e.g., NCOA7-AS) and in grey, those for which very little data is available.