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.

DExH/D-box helicases at the frontline of intrinsic and innate immunity against viral infections

“…In contrast, DDX21 was reported to inhibit IAV RNA synthesis by interacting with the PB1 subunit of the polymerase [76,77]. The DDX21-PB1 interaction is prevented in part by NS1, impairing DDX21 antiviral effect.…”

“…In the context of HIV-1 infection, DDX21 was identified as a binding partner of Rev viral protein, promoting HIV-1 production [75]. In contrast, DDX21 was reported to inhibit IAV RNA synthesis by interacting with the PB1 subunit of the polymerase [76, 77]. The DDX21-PB1 interaction is prevented in part by NS1, impairing DDX21 antiviral effect.…”

Long noncoding RNAs in respiratory viruses: A review

“…ISG20 inhibits the replication of IAV by interacting with viral NP protein and inhibiting viral polymerase activity. [33][34][35] Translation of ISG20 can be regulated by binding miRNA-326 (miR-326) to 3 0 UTR of ISG20 mRNAs. In this regard, Chai et al 23 showed that IAV increases the expression of an interferon-inducible lncRNA termed lnc-ISG20.…”

Peering into Avian Influenza A(H5N8) for a Framework towards Pandemic Preparedness

“…The inclusion of zinc-finger antiviral protein (ZAP, see Figure 4C), given its ability to recognize RNA and antiviral activity of diverse RNA viruses (including IAV) through depleting vRNAs with high frequencies of CG dinucleotides [91][92][93][94] may also provide deeper host-viral interactions. Aside from the discussed host proteins, understanding restriction factors and their mechanism of action are key to the development of therapeutics and prophylactics [95], as exemplified by the autophagy regulator TBC1D5 which controls IAV replication and promote lysosomal targeting of its M2 protein [96] and a natural variant (D130A) in ANP32B which impairs dimeric influenza virus polymerase formation and viral replication [97].…”