Figure 1. SARS-CoV-2 viral proteins inhibit the type I interferon (IFN) signaling pathway. Interferons are responsible for interfering with viral replication and inducing an antiviral state, or immune response, within the host. During viral infection, specific transcription factors, such as NF-kB, stimulate interferons to initiate an immune response. A transcription factor is a protein that controls the activity of a gene and whether it becomes transcribed from DNA to RNA. A) ORF6, ORF8, and N protein are SARS-CoV-2 proteins found to modulate the host immune response. They were found to inhibit NF-kB from binding to interferon promoters to stimulate the type I IFN signaling pathway. This results in a delayed antiviral (IFN) response in the host. 

B) A dual luciferase reporter assay is a biological tool used to study gene expression. This assay was used to test the inhibitory behaviour of ORF6, ORF8, and N protein, infected with Sendai virus, on various promoter (IFN-β, ISRE, and NF-kB) activity. These promoters are involved in stimulating the immune response; therefore, their inhibition would result in a delayed immune response.

C) Upon Sendai virus infection, the ISRE, IFN-β, and NF-kB promoter activity was inhibited by ORF6, ORF8, and N protein as determined by the assay system. This is denoted by the red, blue, and green circles that correspond to the font colour of each respective protein. A recombinant IFN-β protein was used instead of Sendai virus infection to clarify if the viral proteins impaired interferon synthesis or the downstream signals. ORF6 and ORF8 inhibited expression from the ISRE promoter as denoted by the red and blue circles, respectively.

Original Research Study: https://doi.org/10.1016/j.virusres.2020.198074