Antiviral mechanism of BST2. (1) BST2 homodimers restrict the release of mature virions from infected cells by positioning one transmembrane domain in the cellular membrane and the other in the virion membrane. (2) YXY motif in the cytoplasmic tail of BST2 interacts with TRAF2/TRAF6. Together, they recruit TAB1, TAB2, and the activated MAP3K7 kinase complex to induce the phosphorylation of CHUK, IKBKB, and IKBKG, thereby activating the canonical NFKB pathway. (3) BST2 recruits the E3 ubiquitin ligase MARCHF8 to catalyze the ubiquitination of PEDV N protein. The cargo receptor CALCOCO2 then recognizes the ubiquitin chains on N protein and delivers the N protein to autolysosome for degradation.