FIGURE 2.

Role of the N protein in the innate immune processes of host cells. (A) The N protein is a crucial factor that inhibits RNA interference (RNAi) in host cells infected with RNA viruses. It exerts this inhibition through two mechanisms: Firstly, the N protein binds with double-strand RNA (dsRNA) to prevent its recognition and cleavage by Dicer, thus preventing RNAi at the initial stage. Secondly, the N protein can also inhibit RNA degradation caused by small interfering RNA (siRNA) during the effector stage of RNAi. These mechanisms contribute to the stable preservation of viral RNA and enable the replication and proliferation of viruses in host cells, ultimately causing severe damage to them. (B) Viruses use their N proteins to interact with RIG-I and suppress the innate immune response by inhibiting IFN-β production in host cells. This interaction is mediated through the helicase domain of DExD/H-box helicases. SARS-CoV-2’s N proteins inhibit IFN-β by targeting its initial activation step. (C) SARS-CoV-2’s N proteins can impede the host’s innate immune response by functioning as type I interferon (IFN) signaling antagonists, ultimately compromising the immune system’s ability to fight against the virus. Specifically, they inhibit the phosphorylation and nuclear translocation of the transcription factors STAT1 and STAT2. This results in the subsequent attenuation of ISGF3, the IFN-stimulated gene factor 3 transcription complex, and a reduction in the expression of genes that are activated by IFN. Consequently, the presence of N proteins in SARS-CoV-2 infected cells reduces the immune system’s activity, which may increase the severity of the disease in some people.