IAV NS1 and SARS-CoV-2 Nsp1 antagonism of innate immune responses

IAV NS1 and SARS-CoV-2 Nsp1 antagonism of innate immune responses. The induction of innate immune response is initiated by triggering TLRs and RLRs pathways after IAV (red) or SARS-CoV-2 (purple) entrance to susceptible cells. The recognition of PAMPs by PRRs leads to the activation of a signal transduction cascade that involves several modulators, including, among others, TRIF, MyD88, PACT, TRIM25, and Riplet, which leads to the phosphorylation of IRF3/7. Nuclear translocation of phosphorylated IRF3/7 induces the transcription of IFN. Through the Janus kinase (JAK)1 and TYK2 signaling pathway, binding of IFN to the IFNR1/2 receptors leads to the phosphorylation of transcription factors STAT1 and STAT2 which together with IRF9 translocate to the nucleus resulting in the expression of hundreds of ISGs with antiviral activity. Both IAV NS1 (red) and SARS-CoV-2 Nsp1 (purple) can interact with various cellular host factors to inhibit activation of IRF3/7, prevent the maturation and nuclear exportation of cellular mRNA, blocking the loading of cellular mRNA to the ribosomes (Nsp1), or counteracting the antiviral response of different ISGs. This figure was created with Biorender.com

Publication

Antiviral responses versus virus-induced cellular shutoff: a game of thrones between influenza A virus NS1 and SARS-CoV-2 Nsp1 (2024) Ahmed Magdy Khalil, et al. Front Cell Infect Microbiol. 2024;14(NA). Figure: F5. Homo sapiens

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