Current progress on innate immune evasion mediated by Npro protein of pestiviruses

Figures

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  Figure 1. Npro blocks the host’s IFN-activated immune response by degradation of IRF3. Upon viral infection, pathogenic associated molecular patterns (PAMPs) are recognized by cellular pattern recognition receptors (PRRs). A series of cellular pathways were activated subsequently to promote the translocation of phosphorylated IRF3 into the nucleus and initiate the transcription of type I interferon genes by binding to IFN-α/β promoters. Npro could interact with IRF3 before it’s phosphorylation-induced activation, leading to the ubiquitination and proteasomal degradation of IRF-3 and subsequent inhibition of the type I interferon response.

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  Figure 2. N competes with NF-κB to bind with IκBα. Prior to stimulation, NF-κB remains an inactive state in the cytoplasm due to its interaction with IκBα, which masks the unclear localization signals of NF-κB. NF-κB/IκBα complex is activated by phosphorylation in response to various stimuli, such as viral and bacterial pathogens. In this case, IκBα is phosphorylated at Ser32 and Ser36 by the IKKβ subunit following the activation of IKK complex. Then, the E3 ubiquitin ligase complex, SCFβ−TRCP, ubiquitinates IκBα and targets it for degradation by the 26S proteasome, leading to the release of NF-κB for nuclear translocation. However, NF-κB activation induces rapid resynthesis of IκBα, which translocates to the nucleus, dissociates NF-κB from DNA and transports NF-κB to the cytoplasm in a nuclear export sequence-dependent process.