Upon SARS-CoV-2 infection, cytosolic viral dsRNA is recognized by MDA5 and triggers the expression of type I IFN and cytokines; moreover, nsp8 is highly expressed and localized in the cytoplasm of host cells and then interacts with MDA5 CARDs and TRIM4 to form a trimeric complex to shield MDA5 from ubiquitin chains and inhibit TRIM4-mediated K63-linked polyubiquitination, consequently negatively regulates type I IFN signaling and antiviral immune responses, thus favors viral infection and replication. The gene discussed is TRIM4; the disease is viral infectious disease.